Embryology - User contributions [en-gb]

User:Z3417458

2014-10-29T06:58:54Z

Z3417458: /* References */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>
The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>(see these in edit mode).

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> (see these in edit mode) . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
<ref>http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf</ref>

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:57:05Z

Z3417458: /* References */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>
The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>(see these in edit mode).

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> (see these in edit mode) . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
<ref>http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf<ref/>

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:56:54Z

Z3417458: /* References */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>
The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>(see these in edit mode).

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> (see these in edit mode) . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
<ref>http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf<ref/>

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:53:59Z

Z3417458:

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>
The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>(see these in edit mode).

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> (see these in edit mode) . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:50:33Z

Z3417458: /* Lab 10 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>
The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

<ref>https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development<ref/>
https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:48:46Z

Z3417458: /* Lab 11 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>
The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:48:00Z

Z3417458: /* Lab 10 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>

The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:46:01Z

Z3417458: /* Lab 10 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>

The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>PMC4083039</pubmed>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:44:06Z

Z3417458: /* Lab 10 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>

The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>4083039</pubmed>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:43:10Z

Z3417458: /* Lab 10 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

<pubmed>25336194</pubmed>

The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>4083039</pubmed>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:41:33Z

Z3417458: /* Lab 10 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

http://www.ncbi.nlm.nih.gov/pubmed/25336194

The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

<pubmed>4083039</pubmed>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T06:39:03Z

Z3417458: /* Lab 11 Assessment */

==Lab 11 Assessment==
'''1. A recent research article on iPS cells and the main findings of the paper.'''

http://www.ncbi.nlm.nih.gov/pubmed/25336194

The leading cause of death continues to be Cardiovascular disease, there has been a significant amount of research into treatment and the use of different therapies. A key breakthrough has been the research into stem cells and stratergies in regards to regenerative therapy with the use of these cells. There are two types including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Both these cells have great potential for cardiac regeneration. Over time many obstacles have emerged that have proved to be difficult for the development to proceed and to be clinically utalised.

The article presented concentrates on induce pluripotent stem cells and the use in cardiac rgeneration. In order to find a technique to regenerate cardiac tissue with the use of human induced pluripotent stem cells (hiPSCs), a series of methods including tissue engineering and transplatation, and cell preparation need to be discovered. This research article focused on generating hiPSC engineered cardiovascular cell sheets using a new protocol that applies cardiomyocytes (CMs) and vascular cells. These could be promising therapeutic effects among infracted hearts and cardiac regeneration. Physcially intergrated cardiac tissue sheets (hiPSC-CTS) were produced with the cell sheet technology. Improved cardiac functioning was seen in the transplantation of hiPSC-CTS to infracted hearts among rats. The aim was to show that a high potential in cardiac tissue sheets generated from iPSCs could improve cardiac deterioration that precedes myocardial infarction.

The methods that were applied involved a cell- sheet system with the use of a grafted culture surface using a polymer that is temperature responsive. In their previous study with rats, the findings have assisted the development and procedures of this study. Form the observations made it was noted that in order for stem cell based cardiac regeneration to take place, it is important for a co-existence and interaction to occur between CMs and non-monocytes. It was deducted that before such methods are clinically applied, proarrhythmic potentials of iPSC-CTS transplantation need to be evaluated.

In the future iPSCs need to be generated securely with the assurance of minor risks in the possible formation of tumors. This would need to be looked into more carefully prior to any cardiac cell therapy using iPSCs in humans. With these considerations in mind, such therapies could be implemented shortly.
The study was able to demonstrate positive results and thus proved that cardiac regeneration proceeding myocardial infarction could be treated with hiPSCS-derived from cardiac tissue sheet transplantation.

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T05:30:11Z

Z3417458:

==Lab 11 Assessment==

http://www.ncbi.nlm.nih.gov/pubmed/25336194
==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T00:53:46Z

Z3417458: /* Lab Attendance */

==Lab 10 Assessment==
'''1. Research paper on sensory-taste development the research methods and findings.'''

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083039

During development specific regions of the tongue are innervated by axons from gustatory neurons of the geniculate ganglion. The guidance of these axons is controlled by molecular cues in the environment through specific pathways. A number of neurons innervate each taste bud, which are controlled by molecular factors including neurotrophins. Gustatory neurons are regulated by brain derived neurotrophic factors (BDNF), that are manufactured among developing taste papillae and involved in axon guidance. Additionally survival of gustatory neurons is also regulated by Neurotrophin-4 (NT4). These neurotrophins have different functions, both control taste system development and act via the same receptors tyrosine kinase (TrkB) and pan-neurotrophic (p75). The aim of this research article was to observe the neurotrophin receptor p75 and its role in the development of the taste system. The investigation focused on whether p75 is necessary for neuron survival, geniculate ganglion axon guidance and sustaining taste buds throughout embryonic development. A comparison was made between wild type and mutant (p75-/-) mice, tongue innervation patterns and numbers where observed among geniculate ganglion neurons and taste buds.

The methods involved a series of processes including the quantification of geniculate ganglion neurons. Mice were bred for the purpose of this experiment, this involved breeding heterozygous TrkB+/- and p75+/- mice to produce p75-/- and TrkB-/-/p75-/-. Each set of ganglion neurons were labelled according to embryonic days. Ice cold phosphate-buffered paraformaldehyde was used to transcardially perfuse the embryos and then they were post-fixed overnight. The geniculate ganglion neurons were visualised using TUJ-1 antibody and following were a series of other procedures. After this the taste bud quantification was also measured, this involved a series of procedures including OCT medium embedding of tongues, gustatory nerves and taste buds were labelled using anti-cytokeratin 8 and anti-P2X3 antibodes. The volumes of these labelling antibodies were divided to calculate the taste bud volume percentage occupied by innervation. Finally the geniculate ganglia was dil-labelle, using a series of specific processes.

The regulation in the survival of gustatory neurons, axon growth and branching and innervation of taste buds during development are all controlled by brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4). The p75 receptor for BDNF and NT4 is investigated in regards to taste system development.
It was found that innervation of the tongues surface is disrupted during development when p75 is removed. In 75-/- mice the mid region of the tongue was not innervated by the peripheral axons and they also branched less as a result of the deletion of the receptor. Taste buds were lost due to the decrease in tongue surface innervation, as 80% of the remainng taste buds we innervated in p75-/- mice. Therefore it is noted that p75 doesn’t facilitate the role of BDNF in axon guidance. The findings show that p75 doesn’t control BDNF/ NT4 function or a role in gustatory neuron survival, however it does regulate geniculate ganglion axon branching and promotes tongue innervation. Finally it is concluded that additional receptors not involving TrkB and p75 regulate gustatory development.

'''2. Link to the relevant wiki sensory notes page'''

https://embryology.med.unsw.edu.au/embryology/index.php/Sensory_-_Taste_Development

==Lab 9 Assessment==
'''Critical assessment of Group Project Pages'''

'''Group 1 Respiratory'''

Well explained introduction and the histological images provided are great.
In the first section the addition of in text citations would be useful. The content is explained really well and a good use of detail in the paragraphs is not too overwhelming.
Good use of formatting with the inclusion of the table, helps to keep the content clear and concise. The current research, findings and models is present really well, good use of referencing and in text citations. Current findings, models and research is presented really well, good use of referencing and in text citations. Information is clear and with sufficient detail. There are a variety of formatting techniques used which is great to see. Good use of images, however seems to be missing info, suggest filling it out and maybe fixing some of the formatting errors shown but otherwise really well done. This section shows a good amount of research conducted. The historic findings are also well presented, the use of dot points to format the info is very useful and provides clarity. A timeline for the key historic dates might be helpful and another use of visuals. Great to see a variety of abnormalities, shows an extensive research really well presented. Would be great to see more images for this section and maybe drawings too.

This group overall has done really well, there are only a couple of suggestions for the page to be complete these include filling in the missing info under the sub heading ‘current models’. The in text citations and referencing in the first section should be added in to avoid losing marks. Also try adding captions to some of the images, a brief description of what the image is showing. Evidently the research conducted has been quite extensive and the group has worked well to ensure all parts are completed equally. Overall the page is structured really well and organized in an understandable manner. The use of a variety of images and formatting techniques is really great. Just a few minor adjustments and this page will be really great. Great work everyone!

'''Group 2 Renal'''

At the first scroll of this page it already seemed completely sufficiently. The structural layout is done really well and it’s good to see that it’s done according to the advised sub headings. The introduction is really well done, provides a great explanation into renal development, an abundant overview of the whole page and topics that will be addressed.
The info for ‘historic findings’ seems to be lacking content, might be useful to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site.
Might be nice to format a proper timeline or use a table. The ‘current research models’ section is done really well with an abundant amount of detail in each study presented and good use of images. The use of a descriptive caption under each image is done proficiently, it is nice to see that each section has incorporated some form of visual whether histological or from research studies. The ‘kidney’ section is structured really well, the use of the content under early development is unnecessarily but is useful in introducing the stage prior to fetal development. Under the’ anatomical position’ sub heading the in text citations need to be adjusted. For references that are not pubmed use this format; <ref>insert source</ref>. Also the image provided will most likely need to be deleted and then drawn, as we are not allowed to use images directly from textbooks. Just re draw the image if you can and then upload it as you would with any other image. Another suggestion for each of the corresponding organs in renal development, try to format some of the content into dot points or tables so not all lengthy paragraphs. Also noticed one of the images doesn’t have a caption this being under the urethra section. Very well detailed info on the abnormalities, would suggest to add a few more to be completely sufficient.

Lastly, the page has been completed to a high standard in the completion of all the info provided and subsequent images among each section. A few things have been noted, and there are only a few minor modifications that will need to be made these includes; referencing and some formatting as mentioned previously. The use of in text citations throughout the whole page is done efficiently, try to just try keep your references under one main heading. There is great effort noted in the research accumulated so far through the long list of references used to gather the info. Fantastic work everyone, keep up the great work !

'''Group 3 Gastrointestinal'''

This project page has thus far been completed with good effort. The introduction is a good detailed description of the gastrointestinal system consisting of all the corresponding organs. Good to see a timeline of all the events, might be useful to format this into a table since it is so extensive. The ‘recent finding’ section is done well, will however need more info maybe including other studies. Try to look through the GIT development lecture content, there may be some more studies mentioned and these could also refer to others.
The ‘foregut’ section is really well detailed and easy to understand, although it would be nice to see some images, drawings or even tables as done in the ‘midgut’ section. The ‘midgut’ section is great, in its formatting, info, visuals and citations, and the drawings in particular are a really good effort. It would be great if you could try to re-upload the drawings, as it is hard to see some of the labeled structures clearly. In the section describing the ‘hindgut’ there is a good use of in text citations, just be careful as some parts don’t have them so they may need to be added. Also there are some minor formatting adjustments that may need to be made with some of the dot points. Lastly the ‘deformities’ section is done well, easily understandable and a good structural layout. Might want to add a few more, maybe the ‘Anorectal deformities’ sub heading could be moved into the big ‘deformities’ heading.

Finally this page is done well considering there are a number of sections that have to be covered. Some suggestions that could be helpful include; adding an additional heading for historic findings which is listed in our assessment criteria. To help find info for this try to search under the “Explore” tab on the left had side of the embryo page, clicking on the sub heading ‘historic embryo’. Also a useful source is the unsw library as it spans a longer period of time and following the unsw search then research the article in the pubmed site. For the in text citations try to add them after the content rather than before as it’s not clear which parts are from certain references that have been found. Adding some more images especially in the ‘deformities’ section would be good to see. There are only a few minor changes that may need to be addressed. Otherwise you just need to do a little more research to complete the page. So far good work everyone, keep it up. Good luck :)

'''Group 5 Integumentary'''

This page is laid out really well in its organization of each heading and then corresponding subheadings. A well-developed introduction, clearly establishes what will be covered. The development overview is written really well and images are incorporated adequately. The use of a table with images is really good effort, might consider using it on our group page.
Try to be more consistent with the formatting in each subsequent component of the overviews, e.g the ‘nails’ are dot points but then the ‘teeth’ section is a paragraph. This is just a minor observation that could be changed later.
The in text citations seem to be only in some parts of the page, this could be due to the reference not being a pubmed site. Here are some tips that may be helpful with referencing; for the pubmed sites it’s the following format <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for all others its <ref> nsertsource </ref>. Then after those are inserted, add an additional referencing heading and under it write <references/>.

The ‘recent findings’ section is written well, with in depth detail, might want to consider using a few dot points to avoid lengthy paragraphs. Once this section is completely filled with info, it will prove to be really great as it seems a lot of research has been carried out here. There seem to be more referencing issues and the lack of in text citations, try to fix these with the use of the formatting mentioned above. A well written section on ‘historic findings’, again the use of formatting would complete this part. The abnormalities section is done exceptionally well as the cause, risk and management has all been covered. The in text citations are used well as well as the structure of the paragraphs. Some confronting images but well done for finding them for each abnormality, consider adding a few more abnormalities and this will be a really great section.

Finally the work that has been conducted so far is really well done, there are minor adjustments in regards to formatting, referencing and the in text citations. Once these are completed it will look really great. Also some of the sections seems to have info missing, however once this is all filled out it will be sufficient. Good work so far everyone , keep it up and good luck completing the rest of it ☺.

'''Group 6 Endocrine'''

The page is set out really well especially since the endocrine development covers so many organs. It’s a nice clear and concise way of structuring the page. Each particular organ is addressed really well. There is good consistency with each one on the page that is great. The page contains a sufficient about of content and detail in the info for each section of an organ addressed. It is good to see the use of tables and some dot point formatting which always helps to keep the content clear. There are parts in each section that are missing info these include the abnormalities and tables. The use of images with captions containing well detailed descriptions are also constant under each section. Some suggestions to consider include adding more info to the abnormalities would be great. Focusing on discussing what each abnormality is, how it’s contracted, statistics and then treatment. Throughout the whole page in text citations have not been used at all which should be included, especially when research studies are mentioned. A way to assist with this is to use the following format; for pubmed <ref name=PMIDnumber><pubmed>pubmedIDnumber</pubmed></ref> and then for other references <ref>insert source</ref> . Then after those are inserted, add an additional referencing heading and under it write <references/>

Overall the page does not need too many changes, just a few adjustments mostly with formatting and references. Then some sections need a little bit more info to be completed. An introduction would also be a great way to provide an overview of the content that will be covered since there is a lot discussed. So far it can be seen that a great deal of research has been conducted. It’s also understandable that not all sections are completed just yet as this is a pretty lengthy system. Try to also incorporate some graphs, drawings and even video’s, they are a great visual aids. Keep up the good and the page will be really great, good luck :).

'''Group 7 Neural'''

This group page shows a good amount of work completed however there are quite a few sections that clearly still need some more info. A good introduction to the neural development and a accurate description of what will be covered. Although it seems to be missing the in text citations. The section on ‘development during fetal period’ is presented clearly and structured really well. The info is not too overwhelming and the use of dot points for this section is great as neural development is quite complex. There’s a good identification of images and the use of in text citations. The brain development section is written really well with enough detail and it’s nice to see a table for the timeline of changes during each week. It does however seem to be a bit short, maybe that’s because it’s all in dot point form. It would be useful if the ‘brain, spinal cord and meninges development’ were combined under one heading, this might be a better way to structure it. Otherwise just keep each section separate but format the info into paragraph form. In the ‘current research’ section a thorough amount of info was provided. It seems as though it hasn’t been finished and more info will be added later that will be great. The abnormalities content is sufficient and well organised. Just consider using more in text citations in this section, add some more images and complete all the sub headings.

Finally a good effort in this project page, it is structured well and the info provided is easy to understand. However it needs some more research and content to fill all the sub headings in order for it to be finished. Some suggestions that may be considered include; having all the references under one main heading at the end of the page. The use of more in text citations in some of the paragraphs throughout the whole page would be effective. There is an adequately amount of images already shown, so maybe the use of videos or drawings would also be good especially in the abnormalities section and current research. The key is to focus on filing the info and then just making a few adjustments in terms of formatting. Otherwise the page is set out well , just needs a little more work. The page will look really great once completed. Good luck :).

'''Group 8 Musculoskeletal'''

Overall the Group project page seems to be set out quite well with its headings and sub headings. Just needs a bit more info for some of the sub headings particularly from ‘second trimester muscular development’ onwards and a few formatting adjustments. The use of timelines, tables and dot points might help in those sections. The content provided is written well and in a detailed manner, which is still understood. There is a significant amount of research presented and this is seen through the in text citations and then further identified in the reference list. A good use of referencing is seen supporting the content info provided. The content uses examples of past and current research to help develop and establish ideas that are presented well. The abnormalities section on ‘Duchenne muscular dystrophy’ is described really well, maybe other abnormalities could also be added later.

To improve the page some suggestions include the use of diagrams and images, would help to add a bit more vibrancy to the page. Images and drawings are a great way to help in understanding the content. They are also a great way to make the content clearer especially if there are a number of processes involved in the development. Some of the longer paragraphs of content may also be formatted into dot points just to avoid lengthy paragraphs of info. It might also be useful to include some of the headings mentioned on the assessment page (identify current research models and findings, historic findings etc.).
Finally, the page so far is done well however it will need a little bit more work to be completely finished. Try to just gather as much info as you can to ensure you have enough content and then add images and any other visual aids later. Keep up the good work and good luck :).

==Lab 8 Assessment==

'''1. Brief time course and overview of embryonic development of the human ovary'''.

* There are a series of stages in ovarian development these include; germ cell differentiation, continuous follicular growth and continuous follicular atresia
* At the early stages of development the gonads are the same in both sexes, the gonadal ridge forms into the ovary
* The essential genes for the process of ovarian development to occur include Wnt-4 and DAX-1
*Granulosa cells are the cells that provide support in females and the follicle cells are located around the occytes
*Follicle cells undergo proliferation as a result of follicular stimulating hormone among adult cells
*Following ovulation the cells turn into luteal cells in the corpus luteum that secretes hormones estrogen and progesterone
*Theca cells are involved in secreting androstenedione, which has the ability to change follicle cells into estrogens. These cells are located outside the follicle granulosa cells.
*Primordial germ cells during early gastrulation are the first to move via the primitive streak. The hindgut yolk sac junction is where these cells reside. During early development they move to the genital ridge.
* The ovaries are suspended in the broad ligament, at first they are shifted caudally and laterally
*The gubernaculum cause the pelvis to move medially as it attaches to the paramesonephric ducts, it is not condensed
*Some essential hormones in the female reproductive system include gonadotropin-releasing hormone, luteinizing hormone and follicle stimulating hormone

Week 3-4 -----------> At the stage of gastrulation primordial germs cells move

Week 4 -----------> Development of the intermediate mesoderm and pronephros primordium occurs

Week 5 -----------> Mesonephros forms tubules with the aid of the mesonephric duct

Week 6 -----------> Formation of the Uteric bud, metanephros (becomes kidney), genital ridge

Week 7 -----------> Separation process in cloaca, gonadal primordium

Week 8 -----------> Formation of Mullerian ducts (which later develop into the uterus, cervix, fallopian tubes and a third of the vagina. Gonadal differentiation is apparent

Week 9 -----------> The fusion of the paramesonephric duct occurs so the uterus is developed

Week 15 -----------> Primary follicles are developed which establish the ovary

'''2. An image from the historic genital embryology section of the online notes in your description.'''

A historical image of the ovary

Found form https://embryology.med.unsw.edu.au/embryology/index.php/Lecture_-_Genital_Development

[[File:Historic-ovary.jpg|400px]]

==Lab 7 Assessment==

'''1. Recent research paper on the development of the Pancreas'''

The pancreas has two main functions, exocrine involving digestive enzymes and endocrine regulating glucose levels within the blood. There are 3 main stages of development in the pancreas. The primary stage involves initiation of morphogenesis with endodermal evagination<ref name=PMID23603491><pubmed>23603491</pubmed></ref> . Epithelial branching morphogenesis is the secondary stage; in which the basement membrane, differentiating islet progenitors delaminate. Finally at the apices of ductal structures, the formation of acinar cells is commenced. Throughout those stages specific waves of segregation occur with amplication to the endocrine compartment.

The increase in pancreatic endocrine cell population arise at embryonic and pancreatic post-natal growth and regeneraition. There is not much knowledge in the mechanism in endocrine cell expansion throughout the embryonic development. The study concluded through the investigation, that regulating pancreatic endocrine maturation and development is affected by the growth factor-beta (TGF-β) signaling. It is claimed that the process is mediated through the intracellular mediators of TGF- β signaling smad2, smad3 and smad7 expressed during early embryonic pancreatic epithelium. During genetic inactivation two events occur among the intracellular mediators, the smad2 and smad3 increase embryonic endocrine compartment whereas smad7 decrease in embryonic endocrine compartment<ref name=PMID23603491><pubmed>23603491</pubmed></ref>.

From the results the function of smad7 was noted, showing that’s its important in differentiation and maturation of developmental endocrine. The suppression of smad2 &3 was identified as being regulated by smad7 due to their role in expansion of the pancreatic endocrine compartment. This knowledge highlights the mechanisms controlling β-cell development and also shows a connection among replication of pancreatic islets and developmental neogenesis of β-cell development <ref name=PMID23603491><pubmed>23603491</pubmed></ref>. Thus the study illustrated a regulatory point for β- cell expansion among a smad2, 3 & 7 complex. Such finds could have an effective impact on diabetes treatment, through the generation of β-cells and a target in regulating the cells proliferation.

===Reference===
<references/>

'''2. Embryonic layers and tissues that contribute to the developing teeth'''

*Stages include week 6- lamina, week 7- placode, week-8 bud, week 11- cap, week 14- bell
*Contributions from neural crest mesenchyme, ectoderm and mesoderm
*Odontoblasts (secretion of predentin, calcifies for the formation of dentin)
*Ameloblasts (production of enamel)
*Periodontal ligament (CT , supports tooth, contains 'Sharpey’s fibers')

https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Tooth_Development

==Lab 5 Assessment==

===Congenital Diaphragmatic hernia===

A congenital diaphragmatic hernia (CDH) takes place when the diaphragm muscle is unable to close completely during embryo development. As a result the pleuroperitoneal foramen ‘Bochdalek’ (70-75%, posteriorly) fails to seal.
That’s the most common hernia, although it may also occur anteriorly (23-28%) with the foramen of ‘Morgagni’. Therefore any contents of the abdominal viscera; such as the stomach, intestines, spleen or liver can pass through the thoracic cavity while constricting the lung. Due to this the lungs don’t have a large capacity to grow so their development is limited. This can lead to pulmonary hypoplasia or hypertension with further complications also arising.
The incidence of CDH is 1-5:1000 births <ref><pubmed>22214468</pubmed></ref> , it’s a little more common in males.

In the development of the embryo the diaphragm forms during week 8 – 10, it is developed from several components; septum transversum, 3rd and 5th somite, ventral pleural sac, oesophageal mesentery and peritoneal membranes. The diaphragm is innervated by the phrenic nerve which branches of from C3-C5 nerves. The septum transversum anteriorly merges with the oesophageal mesentesry posteriorly connected by the pleuroperitoneal membrane in between them. CDH predominately occurs due to a failure in the fusion process and in past research clinical, genetic and experimental data has shown that during organogenesis there may be disturbances in the retinoid signaling pathway.

To manage the abnormality frequent ultrasonography is performed to observe any further changes throughout development. Prenatal treatments are limited as they can be invasive however there are several that have been developed. There are interuterine processes to allow progress in the lung development. A common strategy is the fetoscopic tracheal occlusion (FETO), involves stimulating the lungs to grow following the closure of the trachea. Postnatal treatment involves ensuring incubation, initiating mechanical ventilation with small volume, high frequency and reduced peak pressure. Attempts are made to repair the diaphragm surgically once cardio-respiratory functions are constant. An early diagnosis is always preferred to ensure prenatal and postnatal management can occur effectively.

====References====
<references/>

<pubmed>12566773</pubmed>
http://ult.sagepub.com.wwwproxy0.library.unsw.edu.au/content/12/1/8.full.pdf

==Lab 4 Assessment==

'''1. Paper on cord stem cells and it's findings'''

<pubmed>24074138</pubmed>

The paper investigates the nature of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum, in patients who suffer from advanced heart failure. There are limitations in the capacity of regeneration for patients with heart failure, when using stem cells this is due to age and disease. The previous use of autologous somatic stem cells in cardiac cell therapy has had limitations, an alternative is juvenile cells which could potentially be more effective. There is some debate whether these juvenile cells would have the capacity to survive transplantation into a failing heart. Since juvenile MSC’s are inhibited in proliferation and their ability to clone as a result of the condition.

It was important to prove that in vitro neonatal cord blood mysenchymal stem cells could be functionally impaired by heart failure serum factors. The study was conducted among healthy volunteers and patients with heart failure, where human serum was required. Through the utilisation of TNF-a and IL-6 measures, the systemic quality of heart failure in sera was verified. The cultivated healthy CB-MSC from neonates were supplemented with protein-normalized human heart failure or control serum. The results illustrated that there was an increase cytokine concentration in heart failure sera, basic MSC properties were sustained when CB-MSC was under heart failure serum conditions. A significant decrease in clonogenic cells occurred with fewer colonies.

A possible treatment option for those who have heart failure is cardiac cell therapy that is still being considered. However it has been difficult to develop new treatments as most studies have been conducted on animals. Therapy in humans based on a cellular level hasn’t depicted major progress in the functioning of the heart. In conclusion the study demonstrated that CB- MSC’s biology is impacted upon through heart disease. This was depicted through the results in proliferation characteristics, stimulation of apoptosis and activation of stress signaling pathways. Furthermore in the experimental process it was found that MSC’s in serum from patients exhibiting heart failure, inhibits the cells proliferation. Future findings could establish specific cell therapies to each patient’s unique response.

'''2. Developmental Vascular shunts include;'''

*Ductus arteriosus, within the aortic arch, blood vessel connects aorta with the pulmonary artery

*Foramen ovale becomes fossa ovalis, located in the heart, in the septum of the atrium, allows blood to flow between the chambers

* Ductus venosus becomes the ligamentum venosum, located in the liver, connects the inferior vena cava to the umbilical vein

==Lab 3 Assessment ==

===Genital Abnormalities===

--[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 21:01, 26 August 2014 (EST)

<<pubmed>24290348</pubmed>>

<<pubmed>25064170</pubmed>>

<<pubmed>23168057</pubmed>>

A review on spermatogenesis and cyptorchidism a common in males, results in an absence of testes either one or both.

<<pubmed>24829558</pubmed>>

--[[User:Z8600021|Mark Hill]] These are all relevant references, and a sentence description for selection would also help. Formatting <nowiki>>></nowiki> should be a single <nowiki>></nowiki>. (4/5)

==Lab 2 Assessment==

==Human zygote==

[[File:Stages in early development of a human zygote.png|850px]]

The stages in early development of a human zygote. All the zygote's matured under in vitro conditions. The original image was cropped to show only Figure A.

===Reference===

<pubmed>19924284</pubmed>

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007844#pone-0007844-g004

--[[User:Z8600021|Mark Hill]] The image is suitable for this assessment, you have included information and formatting here that should only appear with the file summary. I have fixed some formatting issues (see page history for specific changes) and there should have been a better description of the figure identifying the acronyms used in the labelling. (4/5)

==Lab 1 Assessment ==

===Article 1 ===

[http://www.ncbi.nlm.nih.gov/pubmed/24206211 PMID24206211]

<pubmed>24206211</pubmed>

====Summary ====

The research was carried out to identify if ethnicity effects in vitro fertilisation (IVF) treatment and its outcomes. It investigated a larger population (1517) over the period of 5 years, with no similar studies being conducted recently to this extent. A comparison was made between ethnic minority and white European groups and their live birth rate outcomes following IVF or intracytoplasmic sperm injection (ICSI) treatment.

====Method====

*The participants were women who were in completion of their first cycle of IVF or ISCI treatment occurring between 2006 -2011
*Each participant was required to identify their ethnic origin, there were several groups including South East Asians, Middle Eastern Asians, African Caribbeans and white Europeans.
*They were administered gonadotrophin (GnRH) releasing hormone agonists during the midluteal phase of their menstrual cycle.
*Transvaginal ultrasound and serum estradiol measurements were used to observe follicular development. Chorionic gonadotrophin was given if three follicles observed, had a measurement of 18mm or more.
*The occytes were retrieved and then fertilised by IVF or ICSI, following this step at least two embryos were then transferred into the uterus.
*Progesterone pessaries were used for luteal phase support and 16 days later a serum hCG level was used to measure the outcome.
*A transvaginal ultrasound was again used to finally confirm pregnancy and further tests were administered throughout the process, including an ultrasound scan.

====Findings====
The research found that there are significantly higher live birth, clinical pregnancy and implantation rates after IVF treatment in women from the white European group compared to the Ethnic group. From the sub ethnic groups, the South East Asian participants showed the lowest success rates. Further research needs to be conducted to support the results as there were less participants in the sub ethnic minority groups (14.95%) compared to the white European (85.1%).

===Article 2===

[http://www.ncbi.nlm.nih.gov/pubmed/24040458 PMID24040458]

<pubmed>24040458</pubmed>

====Summary====

The paper highlighted the impact of endometriosis on IVF/ICSI treatment outcomes. There was an involvement of 1027 patients, 431 that suffered from infertility due to endometriosis. There have been particularly high risks of infertility due to aspects of endometriosis. This study’s main focus was to see if there were any significant differences in IVF/ICSI treatment outcomes and ovarian stimulation parameters, among women with endometriosis and women with tubal factors.

====Method====

*It included 1027 patients; 152 with stage I-II endometriosis, 279 with stage III-IV endometriosis, 596 patients with tubal factors were the control group.
The study was conducted between 2011 and 2012.
*Patients with endometriosis had complete removal of endometriosis lesion by laparoscopy before their IVF/ICSI treatment. The laparoscopy was also used to diagnose the control group with tubal infertility.

COH Protocol
*Endometriosis patients went through controlled ovarian hyperstimulation (COH) or GnRH-a prolonged protocol.
*Serum E2 level <pg/mL and serum LH level <2mIU/mL were administered in confirmation of pituitary suppression. The GnRH-a long protocol was given to the control group.
*Administration of 150 IU/d intramuscularly was commenced and ovarian stimulation with Puregon or recombinant FSH.
*Once two follicles reached a measurement of 18 mm, recombinant hCG was provided to trigger follicle maturation.
*Oocytes were retrieved transvaginally following hCG injection.
*The assessment of embryos had a few variables; cleavage rate, equality of blastomeres, degree of fragmentation, and mononuclearity in blastomeres.
*The embryos were classified into four categories according to the number of cells and fragmentation percentage.
*From the time of oocyte retrieval luteal phase support was given through 60mg injections of progesterone

====Findings====

The endometriosis patients responded ‘worse’ to the ovarian stimulation that tubal factor patients. Although it was shown that patients with endometriosis had more success rates compared to the patients with infertility as a result of tubal factors. The results depicted that IVF/ICSI is effective for patients who may have infertility due to endometriosis. This was aided by the administration of COH, pituitary suppression, and efficient surgery before the treatments. Without those factors, it is possible that different outcomes would have occurred. The results proved that both patients with endometriosis and tubal infertility had relatively equivalent pregnancy outcomes. Therefore IVF/ICSI (ART) could be an effective treatment for infertility in women due to endometriosis or tubal factors.

--[[User:Z8600021|Mark Hill]] These are appropriate references and good summaries. I have fixed the reference citation formatting. (5/5)

==Lecture Reviews==

===Lecture 1===

I thought the lecture was well divided for a first lecture of the semester. The information about the course and our requirements were well presented and easy to understand. I enjoyed the content about the history of embryology, I've never heard of the "Carnegie Stages of Development". I though that was really interesting to see the development of a zygote and for there to be such technology where you can see such detail is really amazing. I liked that we were shown video's, its always good to have lecture content presented in different ways, keeps me focused.

===Lecture 2===

I've previously learned about the process of meiosis and mitosis in high school biology, it was good to refresh my memory. I was familiar with most of the content since I completed histology in semester 1, so I happy that I could follow the information. The content on polar bodies was new to me, I didn't know what those were before the lecture. The stages of fertilisation for males and females were new to me. In this lecture I found the link between maternal age and the risks of Trisomy 21 surprising as I had no idea that there was a link. It is quite alarming how the risks increase so much with age.

==Type in a Group==

A combination of both of these;

===Teamworker===

A Teamworker is the oil between the cogs that keeps the machine that is the team running smoothly. They are good listeners and diplomats, talented at smoothing over conflicts and helping parties understand one other without becoming confrontational. Since the role can be a low-profile one, the beneficial effect of a Teamworker can go unnoticed and unappreciated until they are absent, when the team begins to argue, and small but important things cease to happen. Because of an unwillingness to take sides, a Teamworker may not be able to take decisive action when it is needed.

===Completer Finisher===

The Completer Finisher is a perfectionist and will often go the extra mile to make sure everything is "just right," and the things he or she delivers can be trusted to have been double-checked and then checked again. The Completer Finisher has a strong inward sense of the need for accuracy, and sets his or her own high standards rather than working on the encouragement of others. They may frustrate their teammates by worrying excessively about minor details and by refusing to delegate tasks that they do not trust anyone else to perform.

==Lab Attendance==

Lab 1 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 12:45, 6 August 2014 (EST)

http://www.ncbi.nlm.nih.gov/pubmed

[http://www.ncbi.nlm.nih.gov/pubmed PubMed]

[http://www.ncbi.nlm.nih.gov/pubmed/25084016 PMID25084016]

<pubmed>25084016</pubmed>
Lab 2 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:11, 13 August 2014 (EST)

Lab 3 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:15, 20 August 2014 (EST)

Lab 4 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 27 August 2014 (EST)

Lab 5 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:03, 3 September 2014 (EST)

Lab 6 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 10 September 2014 (EST)

Lab 7 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:08, 17 September 2014 (EST)

Lab 8 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 24 September 2014 (EST)

Lab 9 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:26, 8 October 2014 (EST)

Lab 10 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:04, 15 October 2014 (EST)

Lab 11 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:17, 22 October 2014 (EST)

Lab 12 --[[User:Z3417458|Z3417458]] ([[User talk:Z3417458|talk]]) 11:53, 29 October 2014 (EST)

User:Z3417458

2014-10-29T00:52:19Z

Z3417458: /* Lab Attendance */

2014 Group Project 9

2014-10-24T11:06:23Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>. The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development. Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>. [[File:Hypospadia classifications.jpg|280px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T11:01:47Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>. [[File:Hypospadia classifications.jpg|280px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:57:13Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular
cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>. [[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:54:27Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>. [[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:51:09Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>. [[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:49:04Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>. [[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:32:25Z

Z3417458: /* Turners Syndrome */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>. [[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:13:46Z

Z3417458: /* Abnormalities */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:09:07Z

Z3417458: /* Abnormalities */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>
[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:06:47Z

Z3417458: /* Abnormalities */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T10:03:39Z

Z3417458: /* Abnormalities */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It is through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>
[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:54:29Z

Z3417458: /* Hypospadias */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|left|thumb|Characteristics presented among men with Klinefelter Syndrome]]

====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:37:06Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|180px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:30:08Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|200px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:28:29Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|200px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:27:22Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|200px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:21:17Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|200px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:15:33Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:10:37Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic,
incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]

====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:08:29Z

Z3417458: /* References */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:05:50Z

Z3417458: /* References */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:04:12Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.
[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:02:44Z

Z3417458: /* True Hermaphroditism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| '''Kallmann syndrome'''

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T09:00:42Z

Z3417458: /* Congenital adrenal hyperplasia */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T08:56:38Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation.
Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

[[File:Ovotestes.jpg|250px|thumb|left|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T08:50:49Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

====Hydrocele====

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

[[File:Ovotestes.jpg|250px|thumb|right|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T08:41:43Z

Z3417458: /* Hydrocele */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

====Hydrocele====
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

[[File:Ovotestes.jpg|300px|thumb|right|Tissue in True Hermaphroditism disorder, showing the Ovotestes that comprises of primary follicles and seminiferous tubules.]]

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

File:Ovotestes.jpg

2014-10-24T08:34:39Z

Z3417458: ==Ovotestes== This is an image drawn my a student showing the tissue in Hermaphroditism disorder, the Ovotestes comprises of primary follicles and testicular tissue consisting of spermatagonia. ==Reference== 3417458 ===Copyright=== Beginning six mon...

==Ovotestes==
This is an image drawn my a student showing the tissue in Hermaphroditism disorder, the Ovotestes comprises of primary follicles and testicular tissue consisting of spermatagonia.

==Reference==

3417458
===Copyright===

Beginning six months after publication, I z3417458 grant the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.

{{Template:Student Image}}

2014 Group Project 9

2014-10-24T08:16:51Z

Z3417458: /* Turners Syndrome */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.
[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

====Hydrocele====
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T07:59:37Z

Z3417458: /* Turners Syndrome */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|400px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists, Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

[[File:Prostate.jpeg|300px|right|thumb|The prostate with the adjoining seminal vesicles and vas deferens]]

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref> <ref><pubmed>18942121</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1611 ||bgcolor="F5FAFF"| Caspar Batholin, described the prostate as a spongy double organ that is continuous with the urethra, secreting protective substances.
|-
|bgcolor="FCFCFC"| 1674 ||bgcolor="FCFCFC"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="F5FAFF"| 1678 ||bgcolor="F5FAFF"| The first illustration of the prostate with the seminal vesicles and seminal ducts attached. This diagram was published by a Dutch anatomist Reinier De Graaf.
|-
|bgcolor="FCFCFC"| 1792 ||bgcolor="FCFCFC"| William Cheselden, an English anatomists and surgeon, challenged the theory that the prostate was two organs, stating that it may in fact be one gland.
|-
|bgcolor="F5FAFF"| 1800 ||bgcolor="F5FAFF"| The double gland idea was disproven with the discovery that the perceived two glands had identical morphology and thus were one gland.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

[[File:Prepuce.jpeg|500px|centre|thumb|The steps of the developing prepuce in the male foetus condensed into three overall events]]

{|class="wikitable mw-collapsible mw-collapsed"
! '''Further information on the historical teachings of the genital system'''
|- bgcolor="F5FFFA"
|
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Human_Embryology_and_Morphology_9 The Urogenital System (1902)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Manual_of_Human_Embryology_19 The Development of the Urinogenital Organs (1912)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Text-Book_of_Embryology_15 The Development of the Urogenital System (1921)]
* [https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.61 The Development of the External Genitalia in the Human Embryo (1921)]
|}

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.

[[File:WomenwithSwyerSyndrome.png|285px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

====Hydrocele====
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T03:45:54Z

Z3417458: /* Swyer Syndrome */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|300px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1674 ||bgcolor="F5FAFF"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.

[[File:WomenwithSwyerSyndrome.png|290px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

====Hydrocele====
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T03:42:40Z

Z3417458: /* Swyer Syndrome */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|300px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1674 ||bgcolor="F5FAFF"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.

[[File:WomenwithSwyerSyndrome.png|300px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|290px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]

===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

====Hydrocele====
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>

2014 Group Project 9

2014-10-24T03:27:17Z

Z3417458: /* Cryptorchidism */

{{ANAT2341Project2014header}}

=Genital=

This page is the second page of the [https://embryology.med.unsw.edu.au/embryology/index.php/2014_Group_Project_4 Group 4 Project]

==Historic Finding==

The development of the genital system has been a focus of scientific research and literature for many centuries, with anatomists publishing articles on both the male and female reproductive system. Historical findings are based mainly on dissections and observation of foetal and deceased neonates in comparison to the current emphasis on molecular research. The different research methods and findings have been published in worldwide journals over hundreds of years, with articles considering the system as a whole or specifically analysing one organ. It through the previous work of these academics that embryology has developed to the complex, abundant study it is today.

{{Historic Disclaimer}}

===Female Genital Development===

Female genital system development has been a subject of many historical literatures dating to the 17th century. Certain research articles aimed to focus on the female genital system as a whole, whereas others delved into specific areas such as the epithelium or specific organs such as the vagina. With the development of technology and research skills over the years, the understanding of the female genital system has improved substantially from the understanding of origin, the structure of the organs and even the nomenclature of the system. <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232984><pubmed>17232984</pubmed></ref>

Majority of the findings lead to a proposal of a theory of that organ or the system, with some of these theories still accepted today while others disproven. The research themes and theories found in historical literature can be divided into three groups. <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

# Those who researched the origin of the vagina and inner genital organs, concluding the origin to be the Mullerian duct.
# Those who focused on the vaginal epithelium, indicating that it arises from part of the Wolffian ducts.
# Those who emphasised the importance of the epithelium of the urogenital sinus in contributing to the vagina.

[[File:Mullerian ducts development.jpeg|300px|right|thumb|Development of Mullerian Ducts into mature female organs]]

Prior to the discovery of the importance of the Mullerian ducts, the origin of the vagina was considered to be the urogenital sinus. It was not until later that century, roughly in 1864 that the Mullerian ducts and their fusion pattern and foetal development was introduced. This realisation was later supported by many academics in their published work, particularly in the early 1900s (1912, 1927, 1930, and 1939). <ref name=PMID13475148><pubmed>13475148</pubmed></ref>

According to the works of the early embryologists Thiersch, Banks, Felix, Bloomfield & Frazer, Hunter and von Lippmann, all who published within the time frame of 1868 to 1939, concluded that the Mullerian (paramesonephric) ducts, found laterally to the Wolffian ducts, are the original structures of the female reproductive organs (the fallopian tubes, uterus and vagina). Initially the foetus contains two Mullerian ducts, however by the ninth week, fusion of the lower portion of the ducts is complete, creating the fundamental structure of the uterus and the vagina, and the non-fused upper part of the ducts emerge into the fallopian tubes. At the time it was also already know that it was not until the fourth and fifth month of development that the uterus becomes continuous with the vagina, with both organs developing a hollow lumen. The muscular layers of the uterus is also present by this stage. The cervix begins to form within the fifth month in between the continuous vagina and uterus. <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID13230915><pubmed>13230915</pubmed></ref>

====The hymen====
[[File:Keibel's model of urogenital organs.jpg|400px|right|thumb|Model depicting the development of the urogenital organs in an eight week old foetus, illustrated by Franz Keibel in 1896.]]

Throughout history the categorisation of the hymen has been debated, with academics either considering this feature as part of or separate to the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. Studies carried out in the 19th century concluded that a hymen was always present in a foetus at full term, even in those with genital disorders such as atresia vaginae, absence or incomplete development of the vagina <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The origin of the hymen has been proposed since the 1800s, with model illustrations from anatomists and embryologists such as Franz Keibel <ref name=PMID17232227><pubmed>17232227</pubmed></ref>. The origin is said to be from the junction of the lower part of the Mullerian duct and the superior portion of the urogenital sinus, an area referred to as the Mullerian eminence <ref name=PMID13475148><pubmed>13475148</pubmed></ref>. The developed hymen has been mentioned in numerous historical published articles, describing the membranous structure as a protruding vertical slit, circular or oblong, and composed of connective tissue and vaginal epithelium <ref name=PMID13475148><pubmed>13475148</pubmed></ref> <ref name=PMID17232227><pubmed>17232227</pubmed></ref> <ref name=PMID17232036><pubmed>17232036</pubmed></ref>.

====The clitoris====

The clitoris, a female organ found anterior to the urethral opening, at the junction of the labia minora, is the most sensitive sexual organ of a female as has been researched for many centuries. In 1896 Berry Hart examined the foetal development of the gland, describing the gland clitorides in the early foetus as bulbous and entire. He proposed that the cells of this gland are epithelial in nature and that a horse-shoe like structure is found surrounding the gland, the prepuce. The prepuce and the clitoris is said to separate at the third month of development when the epithelial cells begin desquamating <ref name=PMID17232227><pubmed>17232227</pubmed></ref>.

The nerve supplying the clitoris, dorsalis clitoridis or dorsal nerve of clitoris, was studied by Yamada in 1950. The nerve was described as containing thick sensory fibres <ref name=PMID14884176><pubmed>14884176</pubmed></ref>. Pacinian corpuscles were also found along the nerve and in the clitoris, however they were simply branched or unbranched. Furthermore, it was discovered that degeneration of the nerve fibre occurs during the foetal period as the intraepithelial nerve fibres in the 10th month foetus was poorer in comparison to the 7th month foetus. <ref name=PMID14884176><pubmed>14884176</pubmed></ref>

===Male Genital Development===

====The Prostate====

The mechanism behind prostate foetal development and modern understanding has been continuously reshaping since the 16th century. Throughout this period, various anatomical classifications have been proposed via dissection procedures, hormone responses and histological methods, attributing to the current understanding of prostate development. The rate of research into the structure and development of the prostate steeply increased in the 20th century, where each decade saw an improvement of the understanding of the development of the gland. <ref><pubmed>18462432</pubmed></ref> <ref><pubmed>13948442</pubmed></ref>

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| 1543 ||bgcolor="FCFCFC"| Andreas Vesalius published the first illustrations of the prostate gland.
|-
|bgcolor="F5FAFF"| 1674 ||bgcolor="F5FAFF"| Gerard Blasius introduced the gland as a structure encircling the neck of the bladder.
|-
|bgcolor="FCFCFC"| 1901 ||bgcolor="FCFCFC"| Pallin thoroughly investigated the prostate gland and its origin.
|-
|bgcolor="F5FAFF"| 1912 ||bgcolor="F5FAFF"| Oswald S Lowsley constructed the first detailed drawing of the anatomy of the prostate by dissecting and researching on a 13-week old foetus, 30-week old foetus, and one at full-term. He proposed the concept of separating the gland into five lobes, and that the prostate originates from the urogenital sinus.
|-
|bgcolor="FCFCFC"| 1920 ||bgcolor="FCFCFC"| Johnson reshaped the anatomical illustration after being unable to replicate Lowsley’s results. He preserved the use of the term ‘lobe’ in describing the prostatic divisions.
|-
|bgcolor="F5FAFF"| 1954 ||bgcolor="F5FAFF"| Three concentric regions became the accepted categorising model of the prostate, as proposed by Franks.
|-
|bgcolor="FCFCFC"| 1983 ||bgcolor="FCFCFC"| McNeal organised the gland into prostatic zones, rejecting the lobe and concentric regions theory.
|}

====Testicular descent====

[[File:Keith1902 fig103.jpg|400px|right|thumb|Representation of the lower foetal abdominal area at 6 months, highlighting the location of the testis prior to descent and the large gubernaculum, in comparison to the testis, attaching the gonads to the scrotum in preparation for testicular descent]]

Testicular descent, which beings during the early foetal period, has been an area of research from the 1700s, when anatomists such as John Hunter began to notice the origin and development of the testicles and their location <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref> <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. The mechanisms behind testicular descent has been debated for at least two centuries, beginning with anatomical dissections on both human and animal foetuses during the eighteenth and nineteenth centuries <ref name=PMID4380018><pubmed>4380018</pubmed></ref> <ref name=PMID4379058><pubmed>4379058</pubmed></ref>, then enhancing with endocrinological discoveries during the twentieth century <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID17104926><pubmed>17104926</pubmed></ref>.

Many theories were proposed and revoked since the discovery of testicular descent. One of the earliest debate was between John Hunter and Albretch von Haller, who concluded that the foetal testis is intra-abdominal and the processus vaginalis remains opened, contrary to the results published by Hunter <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

Hunter’s description of the gubernaculum as a vascular and fibrous foetal structure and the covering cremaster muscle led to further research and numerous theories <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref> <ref name=PMID14172018><pubmed>14172018</pubmed></ref>. Over the years academics mainly disputed the importance of the gubernaculum and the cremaster muscle in both the first and second phase of testicular descent <ref name=PMID14172018><pubmed>14172018</pubmed></ref>.

With the introduction of endocrinology and hormonal testing, the previous historical theories were tested on a cellular basis <ref name=PMID17104926><pubmed>17104926</pubmed></ref>. It has been evidently proven, mainly utilising animal populations, that androgens are important in the descent <ref name=PMID6652187><pubmed>6652187</pubmed></ref>, however it is unclear if it is important in both stages <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>. It is currently accepted that testosterone influences the gubernaculum during the second phase in which the testes reach the scrotum, however the exact method is currently debatable. The first phase theories are under high scrutiny, with theories ranging from the development of the gubernaculum and hormones such as the Mullerian inhibiting substance <ref name=Martyn1991>Martyn P. L. Williams, John M. Huston '''The history of ideas about testicular descent'''. Pediatric Surgery International: 1991, 6(3):180-184</ref>.

{|
|-
|bgcolor="lightskyblue"| '''Date''' ||bgcolor="lightskyblue"| '''Description'''
|-
|bgcolor="FCFCFC"| Late 1700s ||bgcolor="FCFCFC"| Scottish surgeon and anatomist, John Hunter, first documented the gubernaculum and the location of the male foetal testicles.
|-
|bgcolor="F5FAFF"| 1770 ||bgcolor="F5FAFF"| Palleta emphasised that the cremaster muscle was under developed during the time of descent and thus is not an important factor in the process.
|-
|bgcolor="FCFCFC"| 1771 ||bgcolor="FCFCFC"| Pancera considered the cremaster muscle as the key factor in testicular descent.
|-
|bgcolor="F5FAFF"| 1801 ||bgcolor="F5FAFF"| Lobsetin confirmed the findings of Pancera, further highlighting the cremaster muscle. Also suggested that the second phase of testicular descent is complete by birth, influenced by respiration and the increased abdominal pressure that occurs at birth.
|-
|bgcolor="FCFCFC"| 1841 ||bgcolor="FCFCFC"| Curling published his work on the structure of the gubernaculum and the cremaster muscle, concluding that that muscle was important in descending the testis, and subsequent to the descent, the fibres of the muscle everted resulting in it’s new functions of elevating, supporting and compressing of the developed testis.
|-
|bgcolor="F5FAFF"| 1847 ||bgcolor="F5FAFF"| Weber highlighted the processus vaginalis, an embryonic pouch of peritoneum, as the main force of the migration.
|-
|bgcolor="FCFCFC"| 1849 ||bgcolor="FCFCFC"| The theory that descent into the scrotum occurs due to the weight of the testes and muscle associated is introduced.
|-
|bgcolor="F5FAFF"| 1856 ||bgcolor="F5FAFF"| Cleland performed dissections on foetal specimens finding that the foetal gubernaculum did not directly attach the testicle to the scrotum and was only present in the inguinal wall. He presented the theory that the cremaster was not the primary source of descent, second to the gubernaculum.
|-
|bgcolor="FCFCFC"| 1888 ||bgcolor="FCFCFC"| Lockwood proposed a completely unique theory claiming that the testes remained stationary and that it was in fact the surrounding structures that developed, resulting in the changing of the testicular location.
|-
|bgcolor="F5FAFF"| Early 20th Century ||bgcolor="F5FAFF"| Introduction of endocrinology and hormonal testing leading to the theory that the male androgen, controlled by the pituitary gland, influence testicular descent.
|}

====The prepuce====

The development of the prepuce is another genital process that takes place during the foetal phase. It was through medical cases, such as diphtheria <ref name=PMID19971144><pubmed>19971144</pubmed></ref>, presence of adhesions <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, and the most common, congenital phimosis <ref name=PMID20764862><pubmed>20764862</pubmed></ref>, that this penile feature become of interest in medical literature.

Studies from the late 19th century to early 20th century began to focus on the prepuce and discovered the stages of growth and differentiation <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. Conflicting results were obtained throughout this period, with some experiments concluding that this epithelial superficial layer was present and with foetal development, it began degeneration and separation from the enlarging glans, whereas others forwarded the theory that it was the prepuce that eventually grew over a previously exposed penile glans, a theory that was more widely supported <ref name=PMID17104576><pubmed>17104576</pubmed></ref>.

The initial tests carried on the development of the prepuce were able to divide the progress into stages <ref name=PMID20764862><pubmed>20764862</pubmed></ref> <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The stages were ultimately based on the gestational age of the foetus, however this was expressed in terms of the caudal-rostral length of the foetus <ref name=PMID17104576><pubmed>17104576</pubmed></ref>. The construction of stages became accepted as various academics, without collaboration, obtained similar results, organised in a similar method <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

This step-theory explained that each stage correlated to further growth of the prepuce until the glans was completely covered. It also described its origin and highlighted the desquamating and degenerating process of the ectodermal tissue, resulting in the prepuce not being entirely attached to the glans and allowing retraction <ref name=PMID17104576><pubmed>17104576</pubmed></ref>, a process absent in males with adherent prepuce <ref name=PMID20764862><pubmed>20764862</pubmed></ref>.

==Abnormalities==

We discuss both male and female genital abnormalities internally or externally, that may occur during fetal development. The abnormalities have been identified as disorders of sex differentiation(DSD), associated with congenital conditions in the atypical development of chromosomal, gonadal or phenotypical sex <ref><pubmed>16882788</pubmed></ref>, <ref><pubmed>25248670</pubmed></ref>.
The content will cover most common abnormalities and then also the rare cases.
Most genital abnormalities have a high risk in affecting fertility of both sexes.
Currently there are a variety of methods applied to ensure that infertility can be treated and this will be mentioned. All abnormalities may have a specific approach to deal with each case, however management strategies are combined with the addition of psychological treatment. It is implemented to allow parents and patients to deal with any distress or issues that these disorders may cause throughout the child's life.

===FEMALE===

[[File:Uterus and Vagina Abnormalities.jpg|400px|right|border|thumb|Abnormalities of the Uterus and Vagina]]
Abnormalities of the Uterus and vagina are cause by inadequate fusion or regression of Mullerian duct may result as the following;

*double uterus and double vagina
*double uterus
*bicornate uterus
*septated uterus
*unicornate uterus
*cervical atresia <ref>Schoenwolf, GC., Bleyl, S.B., Brauer, P.R., Francis-West, P.H., (2008). Larsen's Human Embryology, 4th ed. Chapter 15 Development of the Urogenital System. New York; Edinburgh: Churchill Livingstone, an imprint of Elsevier.</ref>

====Mullerian agenesis====

Mullerian agenesis also known as ‘Mayer-Rokitansky-Kuster-Hauser’ syndrome, vaginal agenesis or Mullerian aplasia, is presented in the absence of the uterus or vagina or in some case even both. This is due to the unsuccessful development of the Mullerian ducts which then causes certain parts of the reproductive system to be underdeveloped. It is present in 1 of 4000-10 000 women. This condition also uses dilation therapy and following the neovaginal approach with the reconstruction of the vagina in its treatment strategies <ref><pubmed>23635766</pubmed></ref>.

====Vaginal agenesis====

Vaginal agenesis is a rare condition involving the underdevelopment of the vagina. It is commonly cause by a combination of Rokitansky (Mullerian agenesis) and androgen insensitivity syndromes <ref><pubmed>21872517</pubmed></ref>. The congenital disorder affects 1 in 5,000 females <ref>http://www.urologyhealth.org/urology/index.cfm?article=50</ref>.
To ensure effectiveness in treatment, it’s advised after or during adolescence, procedures consist of vaginal dilation shown a success rate of 80% and low risks. In cases where such methods are ineffective then vaginal reconstruction is implemented as a final option for patients <ref><pubmed>17995494</pubmed></ref>.

====Turners Syndrome====

A chromosomal disorder occurring among women due to the absence of the whole or part of the sex chromosome (X). The condition is characterized by short stature, cardiovascular malformations, amenorrhea and estrogen insufficiency <ref><pubmed>16849410</pubmed></ref>. It is prevalent in 1 of 2000 live births among females <ref><pubmed>2037286</pubmed></ref>. Management of the syndrome depends on the extent of the condition the individual will present. Therefore treatment will vary, for short stature biosynthetic growth hormone is utalised in growth hormone. The most common cardiac malformations are bicuspid aortic valve, coarctation of the aorta and aortic stenosis that are all surgically treated. Generally patients are advised to see pediatricians, endocrinologists and many other clinicians depending on the severity of the condition, to discuss strategies to manage the syndrome <ref><pubmed>16714725</pubmed></ref>.

[[File:WomenwithSwyerSyndrome.png|300px|thumb|border|right|Comparison of measures among women with Swyer Syndrome and women without it. The measures are uterine cross sectional areas (UXA).]]

====Swyer Syndrome====

Swyer syndrome (46 XY, gonadal dysgenesis) is a type of hypogonadism disorder in which an individual from birth is phenotypically female with unambiguous genital form and normal mullerian structures. The condition is usually observed during adolescence since the gonads have no hormonal or reproductive function amenorrhea occurs and puberty is delayed <ref><pubmed>3182960</pubmed></ref>. The syndrome affects 1 in 30,000 people <ref>http://ghr.nlm.nih.gov/condition/swyer-syndrome</ref>. It has been found that 10-20% of women with this condition have a deletion of the SRY gene in the DNA-binding site.
In other cases the SRY gene is normal however mutations may present in different determining factors. Managing the syndrome consists of hormone replacement therapy (including estrogen and progesterone), to ensure bone mineral density is maintained and uterine size and shape is improved <ref><pubmed>18410658</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| | '''Polycystic Ovarian Syndrome'''
[[File:PolycysticOvarianSyndrome.jpg|300px|right|thumb|The Female reproductive system showing a normal ovary compared to one that is affected by Polycystic Ovarian Syndrome]]
A metabolic endocrine disorder with an immense variety of phenotypes presented. The disorder shows an imbalance in female sex hormones and a resistance to insulin.
Most importantly it affects the female reproductive system, with issues associated with infertility and menstrual irregularities. It is most common in 5-10% of women in their reproductive age <ref>http://www.myvmc.com/diseases/polycystic-ovarian-syndrome-pcos/</ref>. The treatments implemented depend on the clinical manifestations each patient develops.
Insulin-sensitizing agents are among the treatments used these include Metformin, Rosiglitazone and Piglitazone all have shown to be effective <ref><pubmed>23435473</pubmed></ref>.
|}

[[File:Cryptorchidism.jpg|350px|right|thumb|The sites where Cryptorchidism may occur]]
===MALE===

====Cryptorchidism====

Involves the absence of both or single testis to descend into the scrotum, the testes can be ectopic, incompletely descended, absent or atrophic. It is possible that sometimes the cryptrodism may be spontaneously corrected by 3 months of age. The abnormality can occur as a result of a number of factors including maternal, genetic or environmental <ref><pubmed>24683948</pubmed></ref>. The condition is prevalent in 2-4% of infant males <ref>http://livehealthy.chron.com/cryptorchidism-infertility-1080.html</ref>.
The descendence of testis occur in two stages; in the first stage insulin like hormone attaches the testis to the inguinal ring this is through gubernaculum development.
Following is the inguinoscrotal stage that requires testicular androgens <ref><pubmed>18032558</pubmed></ref>.

Treatment includes human chorionic gonadotropin or gonadotroping-releasing hormones, these are not the most beneficial or advised approach.
Surgical repair is intended to apply the safest and least invasive methods, focusing on repositioning the undescended testicle/s to their normal position in the scrotum. Such surgeries are recommended in early life and have proved to be most effective, with 75%+ success. The therapy used to relocate the testis into the scrotum is known as ‘Orchiopexy’, others include one-stage Fowler Stephens and two-stage FS Orchidopecy. However there are concerns with long-term effects which include infertility and testicular cancer later in life as a result of the procedure <ref><pubmed>24857650</pubmed></ref>.

[[File:Hypospadia classifications.jpg|300px|right|thumb|Different locations of the Meatus in Hypospadia]]
====Hypospadias====

In males the most common congenital malformation of the external genitalia is hypospadias, it’s also the second most common developmental disorder. It occurs due to the midline fusion of the male urethra, as a result the urethral meatus is misplaced. There are several sites where this abnormality may occur: granular, penile, penoscrotal, scrotal and perineal. <ref><pubmed>16006950</pubmed></ref> Its believed that genetic factors contribute to the presence of the disorder, however endocrine and environmental factors are also of significance
<ref><pubmed>24936573</pubmed></ref>. Generally occurs in 1 of 125-300 male births <ref>http://www.hypospadiasuk.co.uk/statistics-about-hypospadias/</ref>.
The surgical methods currently used to treat distal hypospadias, include tabularized incised plate and meatal advancement and glansplasty intergrated repair.
For proximal forms two staged procedures are employed. <ref><pubmed>25023236</pubmed></ref>

[[File:Klinefelter.jpg|300px|right|thumb|Characteristics presented among men with Klinefelter Syndrome.]]
====Klinefelter====

Klinefelter is a genetic disorder caused by the addition of an X chromosome among males (47, XXY, XXY,XXXXY, XXYY), due to the inability of the extra chromosomes to detach throughout meiosis. It is believed to have an origin from either parent. The abnormality has a wide range of phenotypic variations, that typically include infertility, small testes, gynecomastia and hypergonadotropic hypogonadism <ref><pubmed>16342850</pubmed></ref>. The disorder occurs among 1 in 500-1,000 male births <ref>http://ghr.nlm.nih.gov/condition/klinefelter-syndrome</ref>. An early diagnosis is important in order for treatment to be commenced right away.
The treatment implemented involves Testosterone replacement therapy, which assists in easing some of the features, although infertility is still an issue.
The fertility options consist of IVF, where males undergo testicular sperm extraction, cryopreservation of sperm containing semen or testicular tissue during adolescence <ref><pubmed>24563893</pubmed></ref>.

====Peyronie's Disease====

The acquired disease occurs due to fibrotic plaque formations in the tunica albuginea of the penis. This leads to sexual dysfunction, a loss in penile flexibility, shortening and penile malformations <ref><pubmed>20497306</pubmed></ref>. The penis is curved upward as a result of the plaque structure. Adult males are at risk of the condition where about 3.2-8.9% are affected among the population <ref><pubmed>3826933</pubmed></ref>. Strategies applied vary in the extent of the deformities; some procedures involve grafting in the lengthening of the penis, plaque removal and prosthesis implantation in erectile dysfunction <ref><pubmed>23435473</pubmed></ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| ''Chordee'''
Chordee is an abnormality in the development of the penis, it may occur in conjunction with hypospadias. The disorder results in the curvature of the penis and erectile dysfunction
<ref>http://www.webmd.com/men/guide/chordee-repair-treatment</ref>. The causes are evident among males with hypospadias, however in cases where hypospadia is absent the causes are not known and haven’t thus far been identified. The condition occurs in about 4-10% of males. There are a variety of methods used to treat the curvatur these include; skin bridge and frenular release, skin release transfer, pitation technique, dermal grafts, corporal rotation and penile disassembly and finally penile torsion. Any surgical techniques are recommended at the first year of life. Through the treatment surgeons focus on ensuring the urethral plate and neurovascular structures are preserved <ref><pubmed>21805016</pubmed></ref>.
|}

===BOTH===

====Congenital adrenal hyperplasia====

The condition is caused by a deficiency in 21-Hydroxylase, a genetic disorder of steroidogenesis. Occurs due to mutations in genes that encode enzymes that take part in adrenal steroid synthesis therefore there is a loss of function <ref><pubmed>18844712</pubmed></ref>. The deficiency is from mutations in CYP21A2, thus the clinical characteristics may vary. In females it results in the ambiguity of the female genitalia, fused labia majora, larger clitoris and common urogenital sinus <ref><pubmed>15964450</pubmed></ref>. Steroid 21-OHD deficiency is examined in-utero and then prenatal treatment with dexamethasone is administered. It occur is about 1 in 15,000 live births <ref>http://www.patient.co.uk/health/congenital-adrenal-hyperplasia-leaflet</ref>. This is a safe method used and decreases the risk of ambiguous genitalia in females <ref><pubmed>20392211</pubmed></ref>. Among males symptoms aren’t present at birth a side from possible penile enlargement and slight hyperpigmentation <ref><pubmed>15964450</pubmed></ref>. Generally male patients also require the administration of glucocorticoid and mineralocorticoid therapies <ref><pubmed>18446680</pubmed></ref>.

====Hydrocele====
[[File:Hydrocele.jpg|300px|thumb|right|A fetal ultrasound showing Hydrocele surrounding the testis]]

Hydrocele occurs when the space between parietal and visceral layers of tunica vaginalis accumulates an abnormal amount of serous fluid. Normally caused by an imbalance in the processes of production and reabsorption of fluid or varicocelectomy. The condition is prevalent in about 1-3% of births <ref><pubmed>http://bestpractice.bmj.com/best-practice/monograph/1104/basics/epidemiology.html</ref>. To manage the condition treatments focus on ensuring draining any excess fluid and inhibiting reaccumulation. Techniques used involve sclerotherapy and hydrocelectomy <ref><pubmed>20548330</pubmed></ref>. In females it is a very rare condition, occurs in the ‘Canal of Nuck’, a part of the inguinal canal containing a section of the processus vaginalis. A swelling is present on the labia major or inguinal ring. Techniques applied to treat the condition in females involve ligation of the processus vaginalis neck and the hydrocele is surgically resected <ref><pubmed>16416273</pubmed></ref>.

====True Hermaphroditism====

True hermaphroditism also known as ovo-testicular disorder of sexual differentiation or ‘true gonadal intersex’, is a rare intersex abnormality in which an individual has both male and female genitalia. The gonads are asymmetrical with ovarian and testicular differentiation combines as ovo-testis or separately on either side <ref><pubmed>3418019</pubmed></ref>. The individual may have XX, XY or both chromosome types. The disorder occur in 1 of 1,500-2,000 births <ref>http://www.isna.org/faq/frequency</ref>.
Treatment involves reconstructive surgery upon each individual case having to choose a gender, this decision has short and long-term consequences.
Each case is determined differently as there are many factors to consider when choosing the gender identity.
This comprises a long process providing parents with support and guidance in making their decision <ref>http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm</ref>.

{| class="wikitable mw-collapsible mw-collapsed"
! Also related include;
|-
| Kallmann syndrome

Kallmann’s syndrome is a heterogenous disease expressed during puberty due to a combination of hypogonadotropic hypogonadism and anosmia. The genetic disease is responsible for infertility and the inability to smell. Seems to have affects on 1 in 10 000 males and 1 in 50 000 females <ref><pubmed>16952059</pubmed></ref>. It occurs during embryonic development at a time in which hypothalamic neurons (gonadotropin-releasing hormones) are unable to migrate into the hypothalamus. Currently there are no available treatments for the olfactory deficit, however among males hormone replacement therapy is implemented with human chorionic gonadotropin, human menopause gonnadotropin and testosterone undecanoate <ref><pubmed>24432625</pubmed></ref>. In females treatment focuses on maintaining and inducing secondary sex characteristics <ref><pubmed>23368665</pubmed></ref>.

====Hypogonadotropic hypogonadism====

The condition results in a failure to secrete gonadotropin such as luteinizing (LH) and follicular stimulating hormones (FSH), which then reduce the gonadotropin levels <ref>http://www.ncbi.nlm.nih.gov/books/NBK1334/</ref> . This indicates possible issues with the hypothalamus or the pituitary gland. It may occur in conjunction with Kallmann’s syndrome or a decreased gonadotropin-releasing hormone (GnRH). The incidence is about 1 in 2,000 births <ref>http://www.rightdiagnosis.com/h/hypogonadotropic_hypogonadism_syndactyly/prevalence.htm</ref>.
In males treatment methods depend on how the condition is presented and whether it’s associated with another abnormality. Generally the therapies may require testosterone in cases with micropenis and to generate spermatogenesis gonadotropin replacement is utalised. Hypogonadotropic Hypogonadism is rare among females, however it may be presented thus similar treatment options are available. Treatments consist of gonadotropins administration of FSH and LH, to ensure successful occyte formation <ref><pubmed>17260221</pubmed></ref>.
|}

==References==

<references/>