Talk:2009 Lecture 16
- Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development. Seifert AW, Bouldin CM, Choi KS, Harfe BD, Cohn MJ. Development. 2009 Dec;136(23):3949-57. PMID: 19906862
- "Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh).....Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis."
- Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum. Seifert AW, Harfe BD, Cohn MJ. Dev Biol. 2008 Jun 1;318(1):143-52. Epub 2008 Mar 21. PMID: 18439576
- Sonic hedgehog signaling from the urethral epithelium controls external genital development. Perriton CL, Powles N, Chiang C, Maconochie MK, Cohn MJ. Dev Biol. 2002 Jul 1;247(1):26-46. http://www.ncbi.nlm.nih.gov/pubmed/12074550 PMID: 12074550]
- Congenital anomalies of the male urethra Terry L. Levin, Bokyung Han, and Brent P. Little Pediatr Radiol. 2007 September; 37(9): 851–862. Published online 2007 May 22. doi: 10.1007/s00247-007-0495-0. PMCID: PMC1950215
- Unique functions of Sonic hedgehog signaling during external genitalia development. Haraguchi R, Mo R, Hui C, Motoyama J, Makino S, Shiroishi T, Gaffield W, Yamada G. Development. 2001 Nov;128(21):4241-50. PMID: 11684660
X Chromosome Inactivation
- X Chromosome Activity in Mouse XX Primordial Germ Cells
Susana M Chuva de Sousa Lopes, Katsuhiko Hayashi, Tanya C Shovlin, Will Mifsud, M. Azim Surani, and Anne McLaren PLoS Genet. 2008 February; 4(2): e30. Published online 2008 February 8. doi: 10.1371/journal.pgen.0040030. PMCID: PMC2233679
- Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells
Mariana de Napoles, Tatyana Nesterova, and Neil Brockdorff PLoS ONE. 2007; 2(9): e860. Published online 2007 September 12. doi: 10.1371/journal.pone.0000860. PMCID: PMC1959243
Primordial Germ Cells
- Reprogramming Primordial Germ Cells into Pluripotent Stem Cells
Gabriela Durcova-Hills, Fuchou Tang, Gina Doody, Reuben Tooze, and M. Azim Surani PLoS ONE. 2008; 3(10): e3531. Published online 2008 October 27. doi: 10.1371/journal.pone.0003531. PMCID: PMC2567847
Fetal Ovary Position
- Size and location of the fetal human ovary. Sulak O, Malas MA, Esen K, Cetin E, Tagil SM. Fetal Diagn Ther. 2006;21(1):26-33. PMID: 16354971
- "OBJECTIVE: To determine the development and the localization of the ovaries during the fetal period. MATERIAL AND METHODS: One hundred and fifty-four ovaries obtained from 77 human fetuses aged between 9 and 40 weeks of gestation were used in this study. Firstly, the shapes and the positions of the ovaries were established. Second, the localization of the ovaries with respect to linea terminalis, ureters, and the iliac arteries were determined. Finally, the dimensions and the weight of the ovaries were measured. FINDINGS: In the fetal period, the ovaries were most commonly almond shaped and had an oblique orientation. In the 1st trimester the midpoint of the long axis of the fetal ovaries were at the level of linea terminalis. In the 2nd and 3rd trimester and full-term fetuses, it was observed that the ovaries were not in ovarian fossa, suggesting that descensus ovary was in progression during these times. During the intrauterine period, the ovaries were most commonly located anterior to the ureters and over the common iliac artery, only to migrate to its final location between the internal and external iliac arteries towards the end of the 40th week. CONCLUSION: We found that the ovaries did not assume the position of the adults at the end of the fetal period, rather continued its descent after the birth. We believe our findings about the fetal ovaries will be useful in obstetrics, fetal pathology, and forensic pathology."
- adult fibromuscular tube with a wall consisting of three layers: the mucosa, muscularis and adventitia
- Mucosa - stratified squamous epithelium (deep stratum basalis, intermediate stratum spinosum, superficial layers of flat eosinophilic cells which do contain keratin but which do not normally form a true horny layer) rests on a very cellular lamina propria (many leukocytes). Towards the muscularis some vascular cavernous spaces may be seen (typical erectile tissue).
- Muscularis - inner circular and outer longitudinal layers of smooth muscle are present. Inferiorly, the striated, voluntary bulbospongiosus muscle forms a sphincter around the vagina.
- Adventitia - adventitia bordering the muscularis is fairly dense and contains many elastic fibres. Loose connective tissue with a prominent venous plexus forms the outer part of the adventitia.
(text modified from UWA Blue Histology)
This section of notes covers genital development. Differences in development are dependent on a protein product of the Y chromosome SRY gene. Mesonephric duct (Wolffian Duct) and paramesonephric (Mullerian Duct) contribute the majority of male and female internal genital tract respectively.
The mesonephric/paramesonephric duct changes are one of the first male/female differences that occur in development, while external genitaila remain indeterminate in appearance for quite a while.
- Differentiation of gonad (Sex determination)
- Differentiation of internal genital organs
- Differentiation of external genital organs
The 2nd and 3rd stages dependent on endocrine gonad. Reproductive development has a long maturation timecourse, begining in the embryo and finishing in puberty. (More? [../Child/puberty.htm Puberty])
Page Links: [#Intro Introduction] | [#Recent Some Recent Findings] | [#Reading Reading] | [#Overview Development Overview] | [#Objectives Objectives] | [#Learn Learning activities] | [#Computer Computer Activities] | [#Movies Movies] | [#References References] | [#Glossary Glossary]
Some Recent Findings
Yamada G, Suzuki K, Haraguchi R, Miyagawa S, Satoh Y, Kamimura M, Nakagata N, Kataoka H, Kuroiwa A, Chen Y. Molecular genetic cascades for external genitalia formation: An emerging organogenesis program. Dev Dyn. 2006 Jul;235(7):1738-52.
"External genitalia are anatomical structures located at the posterior embryonic region as part of several urogenital/reproductive organs. The embryonic anlage of the external genitalia, the genital tubercle (GT) develops as a bud-shaped structure with an initial urethral plate and later urethra. Embryonic external genitalia are considered to be one of the appendages. Recent experiments suggest that essential regulatory genes possess similar functions for the outgrowth regulation of the GT and limb appendages."
Internal Genital Differentiation
- Human Embryology (2nd ed.) Larson Ch10 p261-306
- The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch13 p303-346
- Before We Are Born (5th ed.) Moore and Persaud Ch14 p289-326
- Essentials of Human Embryology, Larson Ch10 p173-205
- Human Embryology, Fitzgerald and Fitzgerald Ch21-22 p134-152
- Developmental Biology (6th ed.) Gilbert Ch14 Intermediate Mesoderm
- UNSW Embryology [../Refer/urogen_ref.htm References]
- Understand the role of the Y chromosome in sex determination.
- Understand the differences in male/female duct develpoment (mesonephric/paramesonephric).
- Compare the development of the cloaca in the male and female.
- Understand the developmental abnormalities in male and female development.
- Study the developmental overview of gonad/genital development.
- Study the early stage 13/14 embryo urogenital region and identify mesonephric duct, genital ridge.
- Study the late stage 22 male embryo urogenital region and identify mesonephric duct, paramesonephric duct, genital tubercle, scrotal swellings.
- Study the early female fetal (week 10) urogenital region and identify paramesonephric duct, mesonephric duct, , ovary, developing uterus/vagina, genital tubercle.
- Watch the animations (listed under movies) of male/female genital development.
|File:E105.jpg[../Movies/genital/germcell.htm Primordial Germ Cell (PGC) migration]||File:Germcell.jpg[../Movies/larsen/germcell.mov Germ Cell Migration] (440 Kb)|
|File:Fe.jpg[../Movies/larsen/fe.mov Female Gonad] (228 Kb)||File:Ma.jpg[../Movies/larsen/ma.mov Male Gonad] (288 Kb)|
|File:Female.jpg[../Movies/larsen/Female.mov Female External] (288 Kb)||File:Male.jpg[../Movies/larsen/Male.mov Male External] (288 Kb)|
|File:Gonad.jpg[../Movies/larsen/gonad.mov Aortic Branches to Glands (Gonads only)] (765Kb)||File:Testes.jpg[../Movies/larsen/testes.mov Testes Descent ](172 Kb)|
- Humans (week 5-6)
- Germ cells migrate into gonadal ridge
- Gonads (male/female) identical at this stage, indifferent
- dependent on sex chromosome
- Y testes
- No Y ovary
- SRY protein (Testes determining factor, TDF) binds DNA
- Transcription factor, Bends DNA 70-80 degrees
Internal Genital Organs
- All embryos form paired
- Mesonephric duct, see kidney development
- Paramesonephric duct, Humans 7th week Invagination of coelomic epithelium Cord grows and terminates on urogenital sinus
- Male Gonad (testes) secretes Mullerian duct inhibitory factor (MDIF) which causes regression of paramesonephric duct
- Male Gonad (testes) secretes Testosterone which retains mesonephric duct
External Genital Organs
- All embryos initially same (indifferent)
- Testosterone differentiates male
The male and female reproductive systems develop initially "indifferently", it is the product of the Y chromosome SRY gene that makes the difference.
There are many different issues to consider in the development of the genital system. Importantly its sex chromosome dependence, late embryonic/fetal differential development, complex morphogenic changes, long time-course, hormonal sensitivity and hormonal influences make it a system prone to many different abnormalities.
There is also growing research interest in the downstream influence of genital development on other systems, such as neurological development.