Difference between revisions of "Lecture - Genital Development"

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=Genital Development=
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{{Header}}
 
== Introduction ==
 
== Introduction ==
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{{2017ANAT2341draftnotice}}
  
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{|
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| This lecture covers embryonic sexual differentiation covering gonad, internal and external genital development.
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Differences in development are dependent on a protein product of the Y chromosome SRY gene. The paired '''mesonephric ducts''' (Wolffian ducts) and '''paramesonephric ducts''' (Müllerian ducts) contribute the majority of male and female internal genital tract respectively.  I will also introduce some abnormalities of development, that will be covered in the associated practical class.
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This is one system that continues to develop and change postnatally with puberty and menopause.
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| width=150px|<center> '''♂''' Male '''♀''' Female </center>
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|}
 
[[File:Human idiogram.gif]] [[File:Historic-testis.jpg|240px]] [[File:Historic-ovary.jpg|240px]]
 
[[File:Human idiogram.gif]] [[File:Historic-testis.jpg|240px]] [[File:Historic-ovary.jpg|240px]]
  
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.
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<br>
 
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[[Media:ANAT2341_2018_-_Lecture_13_-_Beverdam_-_Reproductive_System.pdf|'''Lecture Slides PDF''']]
 
== Objectives ==
 
== Objectives ==
 
* Understand the development of the gonads in males and females
 
* Understand the development of the gonads in males and females
Line 13: Line 23:
 
* Understand the developmental abnormalities in male and female development.
 
* Understand the developmental abnormalities in male and female development.
  
==Textbooks==
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==Lecture Resources==
===The Developing Human: Clinically Oriented Embryology===
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[[Media:ANAT2341_2018_-_Lecture_13_-_Beverdam_-_Reproductive_System.pdf|Lecture PDF]]
{|
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{| class="wikitable mw-collapsible mw-collapsed"
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! colspan=2|Movies &nbsp;
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|-
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| {{Genital cartoons}}
 
|-
 
|-
| [[File:The Developing Human, 9th edn.jpg|90px]]
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|
| '''Citation:''' The Developing Human: clinically oriented embryology 9<sup>th</sup> ed. Keith L. Moore, T.V.N. Persaud, Mark G. Torchia. Philadelphia, PA: Saunders, 2011. (links available to UNSW students)
 
* [http://er.library.unsw.edu.au/er/cgi-bin/eraccess.cgi?url=http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-2002-0..00012-6&isbn=978-1-4377-2002-0&uniqId=330028653-2#4-u1.0-B978-1-4377-2002-0..00012-6 Chapter 12 - Urogenital System]
 
|}
 
===Larsen's Human Embryology===
 
 
{| border='0px'
 
{| border='0px'
 +
! Colspan=3|Mouse Primordial Germ Cell Migration
 
|-
 
|-
| [[File:Larsen's human embryology 4th edn.jpg|90px]]
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| {{Primordial germ cell migration 1}}
| '''Citation:''' Larsen's human embryology 4th ed. Schoenwolf, Gary C; Larsen, William J, (William James). Philadelphia, PA : Elsevier/Churchill Livingstone, c2009. (links available to UNSW students)
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| {{Primordial germ cell migration 2}}
* [http://er.library.unsw.edu.au/er/cgi-bin/eraccess.cgi?url=http://www.mdconsult.com/books/linkTo?type=bookPage&isbn=978-0-443-06811-9&eid=4-u1.0-B978-0-443-06811-9..10015-6 Chapter 15 - Development of the Urogenital System]
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| {{Primordial germ cell migration 3}}
 
+
|}
* [http://er.library.unsw.edu.au/er/cgi-bin/eraccess.cgi?url=http://er.library.unsw.edu.au/er/cgi-bin/eraccess.cgi?url=http://www.mdconsult.com/books/linkTo?type=bookPage&isbn=978-0-443-06811-9&eid=4-u1.0-B978-0-443-06811-9..10017-X Chapter 17 - Development of the Ears and Eyes]
 
 
|}
 
|}
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{| class="wikitable mw-collapsible mw-collapsed"
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! colspan=2|References &nbsp;
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|-
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| {{Embryo logocitation}}
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|
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{{Genital Links}}
  
===Embryology===
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[[ANAT2341 Lab 8]] [https://embryology.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Genital_Development&oldid=248238 2016] | [[Media:Lecture 2016 - Genital Development.pdf|2016 PDF]] | [https://embryology.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Genital_Development&oldid=248022 2015] | [[Media:2015ANAT2341_Lecture_16_-_Genital Development.pdf|2015 PDF]] |
{| border='0px'
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[https://embryology.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Genital_Development&oldid=144824 2014] | [http://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Genital_Development&oldid=125211 2013] | [http://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Genital_Development&oldid=108037 2012] | [http://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Genital_Development&oldid=72414 2011]
 +
|-
 +
| {{MPT2015cover_citation}}
 +
| The following chapter links only work with UNSW Library subscription (with student Zpass log-in).
 +
* [http://ebookcentral.proquest.com.wwwproxy1.library.unsw.edu.au/lib/unsw/reader.action?docID=2074364&ppg=329 Urogenital System]
 +
|-
 +
| [[File:Larsen's human embryology 5th ed.jpg|50px]]{{Larsen2015APAcitation}}
 +
| The following chapter links only work with UNSW Library subscription (with student Zpass log-in).
 +
*  [http://ebookcentral.proquest.com.wwwproxy1.library.unsw.edu.au/lib/unsw/reader.action?docID=2074524&ppg=412 Development of the Reproductive System]
 
|-
 
|-
| [[File:Logo.png|80px]]
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| [[File:Endocrinology - An Integrated Approach.png|50px]] Nussey, S. and Whitehead, S. (2001). ''Endocrinology - An Integrated Approach''. UK Oxford: BIOS Scientific Publishers. ISBN-10: 1-85996-252-1
| Hill, M.A. (2012) <i>UNSW Embryology</i> (12<sup>th</sup> ed.). Sydney:UNSW.
+
| [[Talk:Lecture_-_Endocrine_Development#Endocrinology_-_An_Integrated_Approach|Detailed Table of Contents]] | [http://www.ncbi.nlm.nih.gov/books/NBK22 Bookshelf Link]
 
+
* [http://www.ncbi.nlm.nih.gov/books/n/endocrin/A972/ Chapter 6. The gonad]
{{Genital Links}} | [[2010_Lecture_16|2010 Lecture]]  
 
 
|}
 
|}
  
:'''Links:''' [[Embryology Textbooks]]
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==Stages of Sexual Differentiation ==
  
== Overview - The Four Stages of Sexual Differentiation ==
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# Development of the '''indifferent gonad''' - (genital ridge) early embryo
 
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# Differentiation of gonad - ('''testis or ovary''') late embryo, defining event in sexual differentiation
There are four stages of sexual differentiation, some of which overlap in time. However, the order in which they occur is as follows:
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# Differentiation of '''internal genital organs''' and ducts - late embryo to fetal
 
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# Differentiation of '''external genitalia''' - fetal
# Development of the indifferent gonad - also known as the genital ridge
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# Development of '''secondary sexual characteristics''' - puberty
# Differentiation of gonad into testis or ovary
 
# Differentiation of internal genital organs and ducts
 
# Differentiation of external genitalia and secondary sexual characteristics
 
  
 
[[File:Stage22 mesonephros.jpg|thumb|Stage 22 mesonephros]]
 
[[File:Stage22 mesonephros.jpg|thumb|Stage 22 mesonephros]]
 
====Important Events====
 
 
*The first event in sexual differentiation is the development of the indifferent gonad - sometimes called the bipotential gonad or just "genital ridge"
 
*The first observable sign of sex-specific differentiation in the male is the appearance of testis cords, which are the precursors of the adult seminiferous tubules.
 
*The first observable sign of sex-specific differentiation in the female is the entry of the germ cells into meiosis.
 
*Males and females develop both sets of ducts - those that are used in the male and those that are used in the female -  and therefore have the potential to develop either way.
 
*Sex-specific differentiation of the internal ducts and the external genitalia is entirely controlled by hormones. Therefore, the important defining event in sexual differentiation is whether the gential ridge develops as an ovary or a testis. All other events follow on from that decision.
 
 
[http://www.ncbi.nlm.nih.gov/pubmed/17237341 Reveiw of mammalian sex determination]
 
  
 
[[File:Urogenital indifferent.jpg|240px|Urogenital Indifferent]] [[File:Urogenital male.jpg|240px|Urogenital Male]] [[File:Urogenital female.jpg|240px|Urogenital Female]]
 
[[File:Urogenital indifferent.jpg|240px|Urogenital Indifferent]] [[File:Urogenital male.jpg|240px|Urogenital Male]] [[File:Urogenital female.jpg|240px|Urogenital Female]]
  
 
==Human Timeline==
 
==Human Timeline==
* 24 days - intermediate mesoderm, pronephros primordium
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{|
* 28 days - mesonephros and mesonephric duct
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|
* 35 days - ureteric bud, metanephros, genital ridge
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* '''Week 3-4''' - primordial germ cells migrate during gastrulation
* 42 days - cloacal divison, gonadal primordium - indifferent to first appearance of testis cords
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* '''Week 4''' - (24 days) intermediate mesoderm, pronephros primordium
* 49 days - paramesonephric duct, clear gonadal differentiation
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* '''Week 5''' - (28 days) mesonephros and mesonephric duct
* 56 days - paramesonephric duct fusion (female)
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* '''Week 6''' - (35 days) ureteric bud, metanephros, genital ridge
* 100 days - primary follicles (ovary)
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* '''Week 7''' - (42 days) cloacal divison, gonadal primordium - indifferent to first appearance of testis cords
 +
* '''Week 8''' - (49 days) paramesonephric duct, clear gonadal differentiation
 +
* '''Week 9''' - (56 days) paramesonephric duct fusion (female)
 +
* '''Week 15''' - (100 days) primary follicles (ovary)
 +
| [[File:Amnion 001 icon.jpg|160px|link=Amniotic Cavity Development Movie]]
 +
|}
  
==Kidneys and the urogenital system ==
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==1. Development of the indifferent gonad==
 +
{|
 +
|
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* '''intermediate mesoderm''' - (between somites and lateral plate mesoderm) kidneys and genital ridge develop.
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* '''kidney multiple stages''' - occur in a rostrocaudal sequence
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** '''pronephros''' > '''mesonephros''' > '''metanephros''' (true adult kidney)
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* '''pronephros''' (week 4) earliest structure to form featuring a pronephric duct with associated nephrogenic mesenchyme.
 +
** pronephros degenerates - leaving only the duct system running down to the cloaca ('''mesonephric duct''' = Wolffian duct).
 +
* '''mesonephros''' - next stage a series of mesonephric tubules in the mesenchyme that are induced by the mesonephric duct.
 +
** mesonephros degenerates - in mammals (In fish and amphibians it is the functioning adult kidney).
 +
** In mammals it serves mainly as the site for gonadal development.
 +
| [[File:Mesoderm-cartoon4.jpg]]
 +
|}
  
[[Image:Mesoderm cartoon4.gif]]
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[[File:Urogenital_sinus_001 icon.jpg|160px|link=Urogenital Sinus Movie]] [[File:Adrenal_and_gonad_early_development.jpg|600px]]
* kidneys and genital ridge develop from intermediate mesoderm, which lies between the lateral plate mesoderm and the somites.
 
* kidney develops in multiple stages, which occur in a rostrocaudal sequence; pronephros>mesonephros>metanephros (true adult kidney)
 
* earliest structure to form is the pronephros, in week 4, featuring a pronephric duct with associated nephrogenic mesenchyme.
 
* pronephros degenerates early on, leaving only the duct system running down to the cloaca – this becomes known as the mesonephric duct (Wolffian duct), in the embryo.
 
* next stage is the formation of the mesonephros, a series of mesonephric tubules in the mesenchyme that are induced by the mesonephric duct.
 
* mesonephros is a transient structure in mammals. In fish and amphibians it is the functioning adult kidney but in mammals it serves mainly as the site for gonadal development.
 
  
==Chromosomal Sex Determination==
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Gonad and adrenal early development (not required to know molecular information)
  
[[File:Y_chromosome.jpg|right]]
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==2. Differentiation of gonad into testis or ovary==
 +
===Chromosomal Sex Determination===
  
===History===
+
{| width=800px|
* 1916 Thomas Morgan and Calvin Bridges write ''Sex-linked inheritance in Drosophila'' and show that sex is determined by the X:autosome ratio
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! Males
* 1923 Theophilus S Painter describes the ''Chromosomes of Man'' -  23 autosomes plus an X and a Y - it is assumed that sex determining mechanism will be the same as ''Drosophila''
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! Females
* 1959 Ford et al. find a human XO and female - Turner's syndrome
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|-
* 1959 Jacobs and Strong find an XXY male - Kleinfelter's syndrome
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|  valign=top|[[Y Chromosome]]
* Together these prove that the Y chromosome determines sex and not the X:autosome ratio
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* 59 million base pairs, hypervariable in length, mostly non-functional repeats
* 1989 XX males found that carry a very small portion of Y chromosomal DNA (60kb)
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* Current known protein-coding genes = 48 including ''SRY''  
* Using DNA from these males a search for the testis determining gene, ''TDF'' or ''TDY'' led to the isolation of the gene now calles ''SRY'' because it comes from the '''S'''ex-determining '''R'''egion of the '''Y''' chromosome. It is the molecular "switch" that determines sex in humans.
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* ''SRY'' encodes a 204 amino acid protein (TDF) that is a member of the HMG (High mobility group) box class of DNA-binding proteins. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes.
 
+
|  valign=top|[[X Chromosome]]
===Y chromosome ===
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* 155 million base pairs, contains about 5% of the haploid genome and encodes house-keeping and specialized functions.
[http://www.ensembl.org/Homo_sapiens/Location/Chromosome?r=Y:29030931-29130931 Y Chromosome]
 
* Y chromosome - 59 million base pairs, hypervariable in length, mostly non-functional repeats
 
* Current known protein-coding genes = 62 including ''SRY''  
 
* ''SRY'' encodes a 204 amino acid protein that is a member of the HMG (High mobility group) box class of DNA-binding proteins. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes.
 
 
 
===X chromosome===
 
[http://www.ensembl.org/Homo_sapiens/Location/Chromosome?r=X:81932856-82032856 X chromosome]
 
* 155 million base pairs  
 
* In contrast to the Y chromosome, the X chromosome contains 815 known protein coding genes - about 5% of the haploid genome and encodes house-keeping and specialized functions.  
 
 
* Genes such as Wnt-4 and DAX-1 necessary for initiation of female pathway ovary development
 
* Genes such as Wnt-4 and DAX-1 necessary for initiation of female pathway ovary development
* An early discovery (1961) was that in order to have correct levels of X chromosome gene/protein expression (gene dosage), females must "inactivate" a single copy of the X chromosome in each and every cell. The initiator of the X inactivation process was discovered (1991) to be regulated by a region on the inactivating X chromosome encoding an '''X''' '''i'''nactive '''s'''pecific '''t'''ranscript (XIST), that acts as RNA and does not encode a protein.
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|-
* The genetic content of the X chromosome has been strongly conserved between species because these genes have become adapted to working as a single dose - Ohno's law (Ohno S (1967). Sex Chromosomes and sex-linked genes).
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| [[File:Human_Y_chromosome_SRY_region.jpg|200px|link=Y Chromosome]]
* X inactivation occurs randomly throughout the embryo, generating a mosaic of maternal and paternally derived X chromosome activity in all tissues and organs. This can be seen in the fur colour of tortoiseshell cats.
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| [[File:Human_X_chromosome.jpg|300px|link=X Chromosome]]
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|-
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|
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|  [[Molecular_Development_-_X_Inactivation|X inactivation]]
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* one X chromosome randomly inactivated throughout the female embryo.
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* mosaic of maternal and paternally derived X chromosome activity in all tissues and organs.
 +
|}
  
[http://en.wikipedia.org/wiki/File:Tortoiseshell_Cat.jpg - Tortoiseshell cat]
+
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK26940/figure/A3716 MBoC - Figure 20-18. Influence of Sry on gonad development] | [http://www.ncbi.nlm.nih.gov/books/NBK26940/bin/ch20f18.jpg image] (image provides a good overview of the anatomy of sex determination, I will refer to this in the lecture and practical class)
 
+
===Supporting Cells===
==Cellular mechanism of sex determination==
 
[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.3716 MBoC - Figure 20-18. Influence of Sry on gonad development]
 
 
 
===The supporting cells===
 
 
* So called because they "support" the germ cells
 
* So called because they "support" the germ cells
Males
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{| width=800px|
* In the male they develop as Sertoli cells
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! Males
* SRY is expressed in the supporting cells and the immediate result is to transform them into Sertoli cells that surround the germ cells and form testis cords
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! Females
* SRY is not expressed in the other cell types of the gonad - therefore the Sertoli cells instruct the germ cells and the steroid secreting cells to take the male path of development
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|-
* Embryonic Sertoli cells secrete anti-Mullerian hormone (AMH)
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|  valign=top|Sertoli cells
* Adult Sertoli cells line the inside of the seminiferous tubules and support spermatogenesis.
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* SRY is expressed in the primordia of the supporting cells, transforming them into Sertoli cells that surround the germ cells and form testis cords
 
+
** SRY is not expressed in the other cell types of the gonad
[http://www.ncbi.nlm.nih.gov/books/NBK10095/figure/A4691/ - adult Sertoli cells]
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* Sertoli cells instruct the germ cells and the steroid secreting cells to take the male path of development
 
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| valign=top|Granulosa cells
[http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Seminiferous-tubule-HEx40.jpg - section of seminiferous tubule]
 
 
 
Females
 
* In the female they develop as follicle cells (granulosa cells)
 
 
* Follicle cells surround and nurture the developing oocytes
 
* Follicle cells surround and nurture the developing oocytes
* In response to FSH, follicle cells proliferate  
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|-
* After ovulation, these cells become luteal cells of the corpus luteum secreting progesterone and oestrogens
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| [[File:Seminiferous-tubule-HEx40.jpg|200px]]
 +
| [[File:Ovary_follicle_01.jpg|200px]]
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|-
 +
|
 +
* embryonic cells - secrete anti-Mullerian hormone (AMH)
 +
* adult cells - line the inside of the seminiferous tubules and support spermatogenesis.
 +
|
 +
* adult cells - in response to FSH, follicle cells proliferate  
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** After ovulation, these cells become luteal cells of the corpus luteum secreting progesterone and estrogen
 +
|}
  
[http://www.ncbi.nlm.nih.gov/books/NBK26857/figure/A3500/ - follicle cells support the oocyte]
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===Steroid secreting cell lineage===
 +
{| width=800px|
 +
! Males
 +
! Females
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|-
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|  valign=top|Leydig cells
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* (interstitial cells) that sit outside the seminiferous tubules
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* Secrete '''testosterone''' in response to luteinizing hormone from the pituitary
 +
|  valign=top|Theca cells
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* that sit outside the follicle granulosa cells
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* Secrete '''androstenedione''' that can be converted by the follicle cells into estrogens
 +
|-
 +
| [[File:Testis_histology_2.jpg|200px]]
 +
| [[File:Ova20he.jpg|200px]]
 +
|}
 +
===Primordial Germ Cells===
 +
[[File:Stage9_bf2-primordial_germ_cell_region.jpg|thumb|Primordial germ cell region (Stage 9)]]
 +
[[File:Stage 13 image 086.jpg|thumb|Genital Ridge (Stage 13)]]
 +
* Primordial germ cells (PGCs) are thought to be the first population of cells to migrate through the primitive streak in early gastrulation (week 3)
 +
* cells then lie at the hindgut yolk sac junctional region
 +
* later migrate into the genital ridge (germinal ridge) in early embryonic development.
  
[http://www.ncbi.nlm.nih.gov/books/NBK10008/figure/A4716/?report=objectonly - ovulation and the menstrual cycle]
+
{| border='0px'
 +
! Colspan=3|Mouse Primordial Germ Cell Migration
 +
|-
 +
| {{Primordial germ cell migration 1}}
 +
| {{Primordial germ cell migration 2}}
 +
| {{Primordial germ cell migration 3}}
 +
|}
  
===The steroid secreting cell lineage===
+
* '''Not the primordial germ cells which respond to SRY''' presence or absence, but the supporting cells within the developing gonad.
Male
+
** Germ cells occasionally migrate by mistake into the developing adrenal gland and in the absence of sertoli cells telling them what to do, abnormally begin to develop as oocytes, even in males
* Develop into Leydig cells which sit outside the seminiferous tubules
 
* Secrete testosterone in response to luteinizing hormone from the pituitary
 
  
Female
+
:'''Links:''' [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=dbio&part=A4665&rendertype=figure&id=A4669 Germ cell migration pathway]
* Develop into theca cells that secrete androstenedione which can be converted by the follicle cells into estrogens
 
  
===Primordial Germ Cells===
+
===Gametogenesis===
[http://embryology.med.unsw.edu.au/Movies/genital/germcell.htm Primordial Germ Cell Migration]
+
* forming PGCs as a small population of migratory cells
 +
* enter the gonad where they undergo several rounds of mitotic cell division
 +
* female - the germ cells enter meiosis and become arrested at the dictyate (diplotene) stage of meiotic prophase 1. All oocytes are at this stage at birth
 +
* male - the germ cells are enclosed by the developing Sertoli cells and are induced to arrest differentiation and cell division as T1 prospermatogonia until after birth.  
  
*  thought to be the first population of cells to migrate through the primitive streak in early gastrulation.  
+
:'''Links:''' [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A3729&rendertype=figure&id=A3735 Image - Spermatogenesis] | [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=dbio&part=A4695&rendertype=figure&id=A4715 Image -Oogenesis]
* This population of cells then lie at the hindgut yolk sac junctional region and later migrate into the genital ridge (germinal ridge) in early embryonic development.
 
* It is not the primordial germ cells which respond to SRY presence or absence, but the supporting cells within the developing gonad.
 
* Germ cells sometimes migrate by mistake into the developing adreanl gland and in the absence of sertoli cells telling them what to do, they begin to develop as oocytes, even in males
 
  
[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=dbio&part=A4665&rendertype=figure&id=A4669 Germ cell migration pathway]
+
==3. Differentiation of internal genital organs and ducts==
 +
[[File:Stage_22_Urogenital_1l.jpg]]
  
===Gametogenesis===
+
Human embryo (Carnegie stage 22, week 8) pelvic level cross-section.
* forming PGCs as a small population of migratory cells
+
===Male===
* enter the gonad where they undergo several rounds of cell division
+
{|
* in the female the germ cells enter meiosis and become arrested at the dictyate (diplotene) stage of meiotic prophase. All oocytes are at this stage at birth
+
| valign="top" | This looped animation shows the development of the male gonad showing medullary sex cords.
* in the male, the germ cells are enclosed by the developing Sertoli cells and are induced to arrest differentiaiton and cell division as T1 prospermatogonia until after birth.
 
[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A3729&rendertype=figure&id=A3735 Spermatogenesis]
 
[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=dbio&part=A4695&rendertype=figure&id=A4715 Oogenesis]
 
  
==Differentiation of internal genital organs and ducts 1. Male==
+
* The paramesonephric duct (red, left) degenerates under the influence of anti-Mullerian hormone (AMH) secreted by sertoli cells.
[[Media:Male_gonad_2.mov‎]]
 
This looped animation shows the development of the male gonad.
 
 
 
* The paramesonephric duct (red, left) degenerates under the influence of anti-Mullerian hormone (AMH) also known as Mullerian inhibiting substance (MIS)or Mullerian duct inhibitory factor (MDIF) secreted by sertoli cells.
 
 
* The mesonephric duct (purple) is maintained and differentiates under the influence of Testosterone secreted by Leydig cells. Within the testes these mesonephric tubules grow towards the testis cords and will form the rete testis. The mesonephric duct extending out of the gonad forms the ductus deferens.
 
* The mesonephric duct (purple) is maintained and differentiates under the influence of Testosterone secreted by Leydig cells. Within the testes these mesonephric tubules grow towards the testis cords and will form the rete testis. The mesonephric duct extending out of the gonad forms the ductus deferens.
* The testis cords (orange) containing the Sertoli cells and the germ cells (which are arrested as T1 prospermatogonia until after birth) later differentiate into seminiferous tubules which become hollow and actively produce spermatazoa after puberty.
+
* The testis cords (orange) containing the Sertoli cells and the germ cells (which are arrested as T1 prospermatogonia until after birth) later differentiate into seminiferous tubules which become hollow and actively produce spermatazoa during puberty.
  
 
The tunica albuginea (white) covers the testis and bands extend inward to form connective tissue septa.
 
The tunica albuginea (white) covers the testis and bands extend inward to form connective tissue septa.
 +
| valign="bottom"|{{Testis movie}}
 +
|}
  
 
===Anti-Mullerian Hormone===
 
===Anti-Mullerian Hormone===
Line 181: Line 220:
 
* In females, it is produced after puberty by follicle cells and suppresses the development of other primary follicles, thus restricting the number of follicles stimulated by FSH.
 
* In females, it is produced after puberty by follicle cells and suppresses the development of other primary follicles, thus restricting the number of follicles stimulated by FSH.
  
==Differentiation of internal genital organs and ducts 2. Female==
+
===Female===
[[File:Infant ovary.jpg|thumb|Infant ovary]]
+
{|
[[File:Oocytenumber.jpg|thumb|human oocyte number]]
+
| valign="top" | This looped animation shows the development of the female gonad showing cortical sex cords.
[http://embryology.med.unsw.edu.au/embryology/images/8/8b/Female_gonad_2.mov Female movie] This looped animation shows the development of the female gonad.
 
  
 
* The mesonephric duct (purple) degenerates, small remnants may remain as epoophoron and paroophoron (in the mesentry of the ovary) and Gartner's cycts (near vagina).
 
* The mesonephric duct (purple) degenerates, small remnants may remain as epoophoron and paroophoron (in the mesentry of the ovary) and Gartner's cycts (near vagina).
Line 190: Line 228:
 
* After entry of the germ cell into meiosis they are called oocytes and they are surrounded by the derivatives of the supporting cell lineage - the follicle cells or granulosa cells.
 
* After entry of the germ cell into meiosis they are called oocytes and they are surrounded by the derivatives of the supporting cell lineage - the follicle cells or granulosa cells.
 
* About 95% of the germ cells that entered meiosis in the female will be lost by a process called follicular atresia (see graph. Only about 400,000 remain at the time of puberty.
 
* About 95% of the germ cells that entered meiosis in the female will be lost by a process called follicular atresia (see graph. Only about 400,000 remain at the time of puberty.
[[File:Stage_22_Urogenital_1l.jpg|thumb]]
 
[[File:Paramesonephric_duct.jpg|thumb|Paramesonephric duct]]
 
  
* Week 7 – duct regression or preservation begins
+
[[File:Infant ovary.jpg|300px]] [[File:Human_ovary_non-growing_follicle_model.jpg|300px]]
Vagina Development
+
| valign="bottom"|{{Ovary movie}}
[http://embryology.med.unsw.edu.au/Medicine/BGDlabXYXX_4.htm Uterus and vagina]
+
|}
 +
 
 +
===Uterus Development===
 +
 
 +
* '''Week 7''' – duct preservation or regression begins
 +
 
 +
[[File:Uterus_001 icon.jpg|100px|link=Development_Animation_-_Uterus]] [[File:Paramesonephric_duct.jpg|300px]] [[File:Newborn_uterus.jpg|400px]]
 +
 
 +
Paramesonephric duct development
 +
 
 +
===Vagina Development===
 +
 
 +
* The embryonic origin of the vagina has been a historically hotly debated issue with several different contributions and origins described.
 +
* Current molecular studies show the whole vagina is derived from the intermediate mesoderm-derived Müllerian duct (see review <ref><pubmed>19598112</pubmed></ref>)
 +
**  bone morphogenic protein 4 (BMP4) reshapes the duct into the vaginal primordium.
 +
* exhibits different features from the uterus
 +
** stratified squamous epithelium
 +
** insensitivity to anti-Müllerian hormone
 +
 
 +
:'''Links:''' [[Vagina Development]]
  
==External Genitalia==
+
==4. Differentiation of External Genitalia==
[http://embryology.med.unsw.edu.au/Medicine/BGDlabXYXX_4.htm External Genital] | [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=endocrin&part=A972&rendertype=box&id=A1026 Endocrinology - Diagram of the development of the external genitalia]
+
[[File:Gray1119.jpg|thumb|Historic diagram of external development]]
 +
[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=endocrin&part=A972&rendertype=box&id=A1026 Endocrinology - Diagram of the development of the external genitalia] | [http://www.ncbi.nlm.nih.gov/books/NBK29/bin/ch6fb5.jpg image]
  
* The external genitalia are initially identical and undergo male and female differentiation under the influence or absence of steroidal sex hormones.
+
* external genitalia are initially identical and undergo male and female differentiation under the influence or absence of steroidal sex hormones.
 
* Indifferent stage ‐ cloaca divided by proliferating mesenchyme forming the urorectal septum which separates the ventral urogenital sinus from the dorsal rectum.
 
* Indifferent stage ‐ cloaca divided by proliferating mesenchyme forming the urorectal septum which separates the ventral urogenital sinus from the dorsal rectum.
 +
* Difference stage ‐ locally in this region the presence or absence of '''dihydrotestosterone''' (DHT), generated from testosterone, determines male/female development.
  
[http://embryology.med.unsw.edu.au/embryology/index.php?title=Development_Animation_-_Urogenital_Septum Urorectal septum and division of the cloacal membrane]
+
===Dihydrotestosterone (DHT)===
 +
[[File:Testosterone_metabolism.jpg|thumb|Testosterone metabolism]]
 +
* Male presence of DHT
 +
** locally in this region leads to '''genital tubercle''' growth, form
 +
** '''genital folds''' (urethral) initial maintenance and then fusion, forming perineal and penile raphe.
 +
** '''labioscrotal swellings''' (lateral to urethreal folds) become the scrotum.
 +
* Female absence of DHT
 +
** genital tubercle remains small, bends caudally to form the clitoris.  
 +
** genital folds (urethral)  persist, do not fuse, and form labia minora.  
 +
** open urogenital sinus forms a cleft into which urethra and vagina open.
 +
** labioscrotal swellings become the labia majora.
  
* Difference stage ‐ locally in this region the presence or absence of dihydrotestosterone (DHT), generated from testosterone, determines male/female development.
+
===Female===
** Presence‐ DHT locally in this region leads to genital tubercle growth, maintenance and fusion of external male genitalia.
 
** Absence‐ of DHT, genital tubercle remains small, bends caudally to form the clitoris. Urethral folds persist, do not fuse, and form labia minora. The open urogenital sinus forms a cleft into which urethra and vagina open. The labioscrotal swellings become the labia majora.
 
===Female Genitalia Development===
 
 
[[File:Newborn_uterus.jpg|thumb|Newborn uterus]]
 
[[File:Newborn_uterus.jpg|thumb|Newborn uterus]]
 
This looped animation shows the development of external female genitalia from the indifferent external structure, covering the approximate period of week 9 to 12.
 
This looped animation shows the development of external female genitalia from the indifferent external structure, covering the approximate period of week 9 to 12.
 +
{|
 +
| valign="bottom"|{{Urogenital septum movie}}
 +
| valign="bottom"|{{Female external movie}}
 +
| Note the original cloacal membrane becomes separated into the urogenital membrane and anal membrane. The urogenital folds beneath the genital tubercle remain separate (unfused), forming the inner labia minora and second outer skin folds form the larger labia majora either side of the developing vestibule of the vagina. Note at the top of the animation, the changing relative size of the genital tubercle as it forms the glans of the clitoris.
 +
|}
  
[[File:Female_external_001 icon.jpg|90px|link=Development_Animation_-_Genital_Female_External]]
 
[[File:Urogenital_septum_001 icon.jpg|90px|link=Development_Animation_-_Urorectal_Septum]]
 
 
 
Note the original cloacal membrane becomes separated into the urogenital membrane and anal membrane. The urogenital folds beneath the genital tubercle remain separate (unfused), forming the inner labia minora and second outer skin folds form the larger labia majora either side of the developing vestibule of the vagina. Note at the top of the animation, the changing relative size of the genital tubercle as it forms the glans of the clitoris.
 
  
 
===Male Genitalia Development===
 
===Male Genitalia Development===
Line 224: Line 288:
  
  
[[File:Male_external_001 icon.jpg|90px|link=Development_Animation_-_Genital_Male_External]]
+
{{Male external movie}}
  
 
Note the original cloacal membrane becomes separated into the urogenital membrane and anal membrane (identical to female). The urogenital folds beneath the genital tubercle begin to fuse in the midline. The skin folds either side for the scrotum, which too has a midline fusion, the raphe. The scrotal sac is initially empty and is an attachment site for the gubernaculum, descent of the testes begins generally during week 26 and may take several days.
 
Note the original cloacal membrane becomes separated into the urogenital membrane and anal membrane (identical to female). The urogenital folds beneath the genital tubercle begin to fuse in the midline. The skin folds either side for the scrotum, which too has a midline fusion, the raphe. The scrotal sac is initially empty and is an attachment site for the gubernaculum, descent of the testes begins generally during week 26 and may take several days.
  
 
==Gonad Descent==
 
==Gonad Descent==
 
 
* Both kidney and gonads develop retroperitoneally, with the gonads moving into the abdomen or eventually into the scrotal sacs.  
 
* Both kidney and gonads develop retroperitoneally, with the gonads moving into the abdomen or eventually into the scrotal sacs.  
 
* During fetal development the gubernaculum and fetal growth in both male and female, changes the gonads’ relative positions finally reaching their adult locations.
 
* During fetal development the gubernaculum and fetal growth in both male and female, changes the gonads’ relative positions finally reaching their adult locations.
 
  
 
Both female and male gonads undergo anatomical descent.
 
Both female and male gonads undergo anatomical descent.
Line 240: Line 302:
 
* '''Testes''' ‐ two anatomical phases in descent, transabdominal and transinguinal, under the influence of the shortening gubernaculum.
 
* '''Testes''' ‐ two anatomical phases in descent, transabdominal and transinguinal, under the influence of the shortening gubernaculum.
  
[[File:Testis-descent_start.jpg|300px]][[File:Testis-descent_end.jpg|300px]]
+
{|
 
+
| valign="bottom"|{{Testis descent movie}}
The testis (white) lies in the subserous fascia (spotted) a cavity processus vaginalis evaginates into the scrotum, and the gubernaculum (green) attached to the testis shortens drawing it into the scotal sac. As it descends it passes through the inguinal canal which extends from the deep ring (transversalis fascia) to the superficial ring (external oblique muscle). Descent of the testes into the scrotal sac begins generally during week 26 and may take several days. The animation shows the path of a single testis.
+
| [[File:Testis-descent start.jpg|300px]] [[File:Testis-descent end.jpg|300px]]
 
+
|}
[http://embryology.med.unsw.edu.au/Movies/genital/testis2.mov Testis descent movie]
 
  
Incomplete or failed descent can occur unilaterally or bilaterally, is more common in premature births, and can be completed postnatally.  
+
The testis (white) lies in the subserous fascia (spotted) a cavity processus vaginalis evaginates into the scrotum, and the gubernaculum (green) attached to the testis shortens drawing it into the scrotal sac. As it descends it passes through the inguinal canal which extends from the deep ring (transversalis fascia) to the superficial ring (external oblique muscle). Descent of the testes into the scrotal sac begins generally during week 26 and may take several days. The animation shows the path of a single testis.  
  
 
Data from a recent study of male human fetal (between 10 and 35 weeks) gonad position.
 
Data from a recent study of male human fetal (between 10 and 35 weeks) gonad position.
Line 254: Line 315:
 
* 27 to 29 weeks - (16.7%) had not descended to the scrotum
 
* 27 to 29 weeks - (16.7%) had not descended to the scrotum
  
==Postnatal - Puberty==
+
Incomplete or failed descent can occur unilaterally or bilaterally, is more common in premature births, and can be completed postnatally.
 +
 
 +
==5. Postnatal - Puberty==
 
[[File:Puberty_growth.jpg|thumb|Puberty growth]]
 
[[File:Puberty_growth.jpg|thumb|Puberty growth]]
 
Puberty can occur over a broad range of time and differently for each sex:
 
Puberty can occur over a broad range of time and differently for each sex:
Line 261: Line 324:
  
 
The physical characteristics that can be generally measured are: genital stage, pubic hair, axillary hair, menarche, breast, voice change and facial hair.
 
The physical characteristics that can be generally measured are: genital stage, pubic hair, axillary hair, menarche, breast, voice change and facial hair.
 +
 +
===Male===
 +
* Testosterone - adult testes produce about 6-10 mg /day in males (~0.5 mg / day in females) carried in circulation by a specific carrier globulin.
 +
* masculinizing androgen - also at puberty, spermatogenesis in males
 +
* development of secondary sexual characteristics - body and facial hair growth (male pattern baldness)
 +
* anabolic effect - metabolism towards conservation of amino acids, promoting protein synthesis, muscle development
 +
* neural - libido in both sexes, male pattern behaviour
 +
* Sustentacular (Sertoli) cells - produce anti-mullerian hormone (AMH) to puberty.
 +
** '''AMH''' - anti-Müllerian hormone (Müllerian inhibiting factor (MIF), Müllerian-inhibiting hormone (MIH), and Müllerian-inhibiting substance (MIS)).
 +
[[File:Male_testosterone_and_AMH_level_graph.jpg|500px]]
  
 
===Female===
 
===Female===
[[File:XXhpgaxis.gif|thumb|Female HPG Axis]]
+
[[File:XXhpgaxis.jpg|thumb|Female HPG Axis]]
 
In females, menarche (the first menstruation or a period) usually occurs after the other secondary sex characteristics, and will continue until menopause (permanent cessation of reproductive fertility).
 
In females, menarche (the first menstruation or a period) usually occurs after the other secondary sex characteristics, and will continue until menopause (permanent cessation of reproductive fertility).
  
 
The diagram shows the hormonal regulation pathway from the brain to the ovary and subsequent impact on uterine changes during the menstral cycle.
 
The diagram shows the hormonal regulation pathway from the brain to the ovary and subsequent impact on uterine changes during the menstral cycle.
  
LHRH = Luteinizing Hormone-Releasing Hormone, also called gonadotropin-releasing hormone (GnRH). This peptide hormone is a decapeptide (10 amino acids) with a short half life (<15 minutes).
+
* '''GnRH''' = Gonadotropin-releasing hormone (GnRH). This peptide hormone is a decapeptide (10 amino acids) with a short half life (<15 minutes).
 +
* '''LH''' = Luteinizing Hormone
 +
* '''FSH''' = Follicle Stimulating Hormone
  
LH = Luteinizing Hormone
+
A similar endocrine axis is also found for regulation of the male gonad.
  
FSH = Follicle Stimulating Hormone
+
<gallery>
 
+
File:HPG female axis.jpg|Hypothalamus - Pituitary - Gonad (female)
A similar endocrine axis is also found for regulation of the male gonad.
+
File:HPG male axis.jpg|Hypothalamus - Pituitary - Gonad (male)
 +
</gallery>
  
 
===Puberty Abnormalities===
 
===Puberty Abnormalities===
Line 281: Line 357:
  
 
==Sex Differences in Adult and Developing Brains==
 
==Sex Differences in Adult and Developing Brains==
 
+
Brains of males and females differ
* not known significance of brain sex differences
+
* in regions specialized for reproduction
* transient sex differences in gene expression in developing brains may cause permanent differences in brain structure
+
* in other regions (controlling cognition, etc) where sex differences are not necessarily expected
* may prevent as well, by compensating for potentially differentiating effects of sex differences in gonadal hormone levels and sex chromosomal gene expression
+
* differentially susceptible to neurological and psychiatric disease
 
 
* Brains of males and females differ
 
** in regions specialized for reproduction
 
** in other regions (controlling cognition, etc) where sex differences are not necessarily expected
 
** Differentially susceptible to neurological and psychiatric disease
 
  
 
2 sources of sexually dimorphic information
 
2 sources of sexually dimorphic information
 
* complement of sex chromosome genes
 
* complement of sex chromosome genes
 
* mix of gonadal hormones
 
* mix of gonadal hormones
 +
 +
* not known significance of brain sex differences
 +
* transient sex differences in gene expression in developing brains may cause permanent differences in brain structure
  
 
==Abnormalities==
 
==Abnormalities==
 +
Human genital abnormalities are currently described as "'''Disorders of Sex Development'''" (DSD).
 +
 +
Include: chromosomal, gonadal dysfunction, tract abnormalities, external genitalia and gonadal descent.
  
 
===Sex Reversal===
 
===Sex Reversal===
* Where chromosomal sex does not match phenotypic sex i.e. XX males or XY females
+
* Where chromosomal sex does not match phenotypic sex i.e. XX males or XY females.
  
XX males - usually caused by a transfer of some Y chromosome DNA onto the X chromosome
+
'''XX males''' - usually caused by a transfer of some Y chromosome DNA onto the X chromosome
 
* Gonads develop as testes, everything looks normal internally and externally but infertile due to a failure of spermatogenesis
 
* Gonads develop as testes, everything looks normal internally and externally but infertile due to a failure of spermatogenesis
 
* Similar to Kleinfelters syndrome (XXY)
 
* Similar to Kleinfelters syndrome (XXY)
  
XY females - usually steroidal origin
+
'''XY females''' - usually steroidal origin
 
* Main cause is Androgen Insensitivity Syndrome (AIS) Complete (CAIS) Partial (PAIS) and Mild (MAIS) usually caused by mutations of the gene encoding the androgen receptor ''AR'' gene located on the X chromosome
 
* Main cause is Androgen Insensitivity Syndrome (AIS) Complete (CAIS) Partial (PAIS) and Mild (MAIS) usually caused by mutations of the gene encoding the androgen receptor ''AR'' gene located on the X chromosome
 
* 5-alpha-reductase deficiency - again leads to a lack of complete steroidal induction of external genitalia  
 
* 5-alpha-reductase deficiency - again leads to a lack of complete steroidal induction of external genitalia  
 
* Rare mutations in key sex determining genes including deletion or mutations of ''SRY''  
 
* Rare mutations in key sex determining genes including deletion or mutations of ''SRY''  
  
Human genital abnormalities are currently described as "Disorders of Sex Development" (DSD) and include: chromosomal, gonadal dysfunction, tract abnormalities, external genitalia and gonadal descent. [http://embryology.med.unsw.edu.au/Notes/genital2.htm Genital Abnormalities]
 
  
===Congenital adrenal hyperplasia===
+
:'''Links:''' [[Genital System - Abnormalities]]
* impairment of cortisol production by the adrenal cortex, is one of the most common causes of intersex genitalia at birth  
+
 
 +
===Congenital Adrenal Hyperplasia===
 +
* impairment of cortisol production by the adrenal cortex, is one of the most common causes of intersex genitalia at birth.
 
* genetically male (XY) infants born with undervirilized genitalia are often assigned and reared as girls.
 
* genetically male (XY) infants born with undervirilized genitalia are often assigned and reared as girls.
  
Line 329: Line 407:
  
 
===Hydrocele===
 
===Hydrocele===
* Male Hydrocele is a fluid-filled cavity of either testis or spermatic cord, where peritoneal fluid passes into a patent processus vaginalis.
+
* '''Male Hydrocele''' is a fluid-filled cavity of either testis or spermatic cord, where peritoneal fluid passes into a patent processus vaginalis.
* Female Hydrocele is a similar, but rarer, fluid-filled cavity occuring in the female as a pouch of peritoneum extending into the labium majorum (canal of Nuck).
+
* '''Female Hydrocele''' is a similar, but rarer, fluid-filled cavity occuring in the female as a pouch of peritoneum extending into the labium majorum (canal of Nuck).
  
 
===Tract Abnormalities===
 
===Tract Abnormalities===
[[File:Uterine abnormalities.jpg|thumb|Uterine abnormalities]]
+
 
[[File:Unicornate uterus.jpg|thumb|Unicornate uterus]]
 
 
Many different forms
 
Many different forms
 
 
* Uterine: associated with other anomolies, unicornuate uterus
 
* Uterine: associated with other anomolies, unicornuate uterus
 
* Vagina: agenesis, atresia
 
* Vagina: agenesis, atresia
 
* Ductus Deferens: Unilateral or bilateral absence, failure of mesonephric duct to differentiate
 
* Ductus Deferens: Unilateral or bilateral absence, failure of mesonephric duct to differentiate
  
 +
{|
 +
| [[File:Uterine abnormalities.jpg|400px]]
 +
| [[File:Unicornate uterus.jpg|400px|Unicornate uterus]]
 +
|-
 +
| Uterine abnormalities
 +
| Unicornate uterus
 +
|}
  
 
Uterine Duplication (uterus didelphys, double uterus, uterus didelphis) A rare uterine developmental abnormality where the paramesonephric ducts (Mullerian ducts) completely fail to fuse generating two separate uterus parts each connected to the cervix and having an ovary each.
 
Uterine Duplication (uterus didelphys, double uterus, uterus didelphis) A rare uterine developmental abnormality where the paramesonephric ducts (Mullerian ducts) completely fail to fuse generating two separate uterus parts each connected to the cervix and having an ovary each.
Line 351: Line 434:
  
 
==External Genitalia - Hypospadia==
 
==External Genitalia - Hypospadia==
 
+
{|
 +
|
 
* most common penis abnormality (1 in 300) from a failure of male urogenital folds to fuse in various regions and resulting in a proximally displaced urethral meatus.  
 
* most common penis abnormality (1 in 300) from a failure of male urogenital folds to fuse in various regions and resulting in a proximally displaced urethral meatus.  
 
* The cause is unknown, but suggested to involve many factors either indivdually or in combination including: familial inheritance, low birth weight, assisted reproductive technology, advanced maternal age, paternal subfertility and endocrine-disrupting chemicals. Infants with hypospadias should not undergo circumcision.
 
* The cause is unknown, but suggested to involve many factors either indivdually or in combination including: familial inheritance, low birth weight, assisted reproductive technology, advanced maternal age, paternal subfertility and endocrine-disrupting chemicals. Infants with hypospadias should not undergo circumcision.
 +
| [[File:Hypospadia_classifications.jpg|200px]]
  
 +
Hypospadia classifications
 +
|}
 
==Movies==
 
==Movies==
 +
 +
{|
 +
| valign="bottom"|{{Ovary movie}}
 +
| valign="bottom"|{{Testis movie}}
 +
| valign="bottom"|{{Urogenital septum movie}}
 +
| valign="bottom"|{{Female external movie}}
 +
| valign="bottom"|{{Male external movie}}
 +
| valign="bottom"|{{Uterus movie}}
 +
| valign="bottom"|{{Testis descent movie}}
 +
| valign="bottom"|{{Gonad vascular movie}}
 +
|}
  
 
{| border='0px'
 
{| border='0px'
 
+
! Colspan=3|Mouse Primordial Germ Cell Migration
|-
 
| [[File:Urogenital_sinus_001 icon.jpg|90px|link=Development_Animation_-_Urogenital_Sinus]]
 
| [[File:Urogenital_septum_001 icon.jpg|90px|link=Development_Animation_-_Urogenital_Septum]]
 
| [[File:Trigone_001_icon.jpg|90px|link=Development Animation - Trigone]]
 
| [[File:Renal_001_icon.jpg|90px|link=Development Animation - Renal]]
 
|-
 
| [[Development_Animation_-_Urogenital_Sinus|Urogenital Sinus]]
 
| [[Development_Animation_-_Urogenital_Septum|Urogenital Septum]]
 
| [[Development Animation - Trigone|Trigone]]
 
| [[Development Animation - Renal|Renal Nephron]]
 
|-
 
| [[File:Uterus_001 icon.jpg|90px|link=Development_Animation_-_Uterus]]
 
| [[File:Female_external_001 icon.jpg|90px|link=Development_Animation_-_Genital_Female_External]]
 
| [[File:Male_external_001 icon.jpg|90px|link=Development_Animation_-_Genital_Male_External]]
 
| [[File:Testis_001 icon.jpg|90px|link=Development_Animation_-_Testis_Descent]]
 
|-
 
| [[Development_Animation_-_Uterus|Uterus]]
 
| [[Development_Animation_-_Genital_Female_External|Female External]]
 
| [[Development_Animation_-_Genital_Male_External|Male External]]
 
| [[Development_Animation_-_Testis_Descent|Testis Descent]]
 
 
|-
 
|-
 +
| {{Primordial germ cell migration 1}}
 +
| {{Primordial germ cell migration 2}}
 +
| {{Primordial germ cell migration 3}}
 
|}
 
|}
 
  
 
== References ==
 
== References ==
 +
<references/>
 
===Textbooks===
 
===Textbooks===
 
* '''Before We Are Born''' (5th ed.) Moore and Persaud Chapter 14 p289-326
 
* '''Before We Are Born''' (5th ed.) Moore and Persaud Chapter 14 p289-326
Line 390: Line 471:
  
 
===Online Textbooks===
 
===Online Textbooks===
* '''Developmental Biology''' (6th ed.) Gilbert Chapter14 [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=dbio.section.3498 Intermediate Mesoderm]
+
* '''Developmental Biology''' (6th ed.) Gilbert Chapter 14 [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=dbio.section.3498 Intermediate Mesoderm]
 +
* Historic - '''Text-Book of Embryology'''. Bailey, F.R. and Miller, A.M. (1921).  New York: William Wood and Co. [[Book_-_Text-Book_of_Embryology_15#The_Genital_Glands|Chapter 15. The Genital Glands]]
 +
 
 +
===Reviews===
 +
<pubmed>17237341</pubmed>| [http://physrev.physiology.org/content/87/1/1.long Physiol. Rev.] | [[Talk:BGD_Lecture_-_Sexual_Differentiation#Figure_Pages|Figure Links]]
  
 
===Search ===
 
===Search ===
Line 401: Line 486:
 
{{External Links}}
 
{{External Links}}
  
* '''Embryo Images Unit:''' [http://www.med.unc.edu/embryo_images/ Embryo Images Online] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genitaltoc.htm Urongenital Development] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital008.htm Internal Genitalia] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital017.htm Definitive Kidney] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital020.htm External Genitalia]
+
* '''Embryo Images Unit:''' [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genitaltoc.htm Urongenital Development] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital008.htm Internal Genitalia] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital017.htm Definitive Kidney] | [http://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital020.htm External Genitalia]
 +
 
 
* '''Histology:''' [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/MaleRepro/malerepro.htm Male Reproductive System] | [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/femalerepro.htm Female Reproductive System]
 
* '''Histology:''' [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/MaleRepro/malerepro.htm Male Reproductive System] | [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/femalerepro.htm Female Reproductive System]
  
{{2011ANAT2341}}
+
 
 +
{{2017ANAT2341 footer}}
 +
 
 +
[[Category:Genital]][[Category:Male]][[Category:Female]]

Latest revision as of 11:54, 3 September 2018

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Introduction


2017 Students - Please note this draft online lecture content is currently being updated for the current course. This notice removed when update completed.



This lecture covers embryonic sexual differentiation covering gonad, internal and external genital development.

Differences in development are dependent on a protein product of the Y chromosome SRY gene. The paired mesonephric ducts (Wolffian ducts) and paramesonephric ducts (Müllerian ducts) contribute the majority of male and female internal genital tract respectively. I will also introduce some abnormalities of development, that will be covered in the associated practical class.

This is one system that continues to develop and change postnatally with puberty and menopause.

Male Female

Human idiogram.gif Historic-testis.jpg Historic-ovary.jpg


Lecture Slides PDF

Objectives

  • Understand the development of the gonads in males and females
  • Understand the chromosomal basis of sex determination
  • Understand the differences in male/female internal duct develpoment.
  • Understand the origins of the external genitalia
  • Understand the developmental abnormalities in male and female development.

Lecture Resources

Lecture PDF

Movies  
Genital Movies
Urogenital sinus 001 icon.jpg
 ‎‎Renal Overview
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Gonad-icon.jpg
 ‎‎Ovary
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Gonad-icon.jpg
 ‎‎Testis
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Female external 001 icon.jpg
 ‎‎Female External‎‎
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Male external 001 icon.jpg
 ‎‎Male External
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Uterus 001 icon.jpg
 ‎‎Uterus
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Testis 001 icon.jpg
 ‎‎Testis Descent
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Gonad blood 01 icon.jpg
 ‎‎Gonad Vascular
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Mouse Primordial Germ Cell Migration
Primordial germ cell 001 icon.jpg
 ‎‎Germ Cell E9.0
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Primordial germ cell 002 icon.jpg
 ‎‎Germ Cell E9.5
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Primordial germ cell 003 icon.jpg
 ‎‎Germ Cell E10.5
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Mouse Primordial Germ Cell Migration
Primordial germ cell 001 icon.jpg
 ‎‎Germ Cell E9.0
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Primordial germ cell 002 icon.jpg
 ‎‎Germ Cell E9.5
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Primordial germ cell 003 icon.jpg
 ‎‎Germ Cell E10.5
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References  
UNSW Embryology logo
Hill, M.A. (2019). UNSW Embryology (19th ed.) Retrieved February 27, 2020, from https://embryology.med.unsw.edu.au
Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | Female | X | ovary | corpus luteum | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Male | Y | SRY | testis | spermatozoa | ductus deferens | penis | prostate | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital
Historic Embryology - Genital 
1887-88 Testis | 1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1904 Leydig Cells | 1904 Hymen | 1905 Testis vascular | 1909 Prostate | 1912 Prostate | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1921 Urogenital Development | 1921 External Genital | 1927 Female Foetus 15 cm | 1932 Postnatal Ovary | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer

ANAT2341 Lab 8 2016 | 2016 PDF | 2015 | 2015 PDF | 2014 | 2013 | 2012 | 2011

Textbook cover Larsen's human embryology 5th edn.
Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders.
The following chapter links only work with UNSW Library subscription (with student Zpass log-in).
Larsen's human embryology 5th ed.jpgSchoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone. The following chapter links only work with UNSW Library subscription (with student Zpass log-in).
Endocrinology - An Integrated Approach.png Nussey, S. and Whitehead, S. (2001). Endocrinology - An Integrated Approach. UK Oxford: BIOS Scientific Publishers. ISBN-10: 1-85996-252-1 Detailed Table of Contents | Bookshelf Link

Stages of Sexual Differentiation

  1. Development of the indifferent gonad - (genital ridge) early embryo
  2. Differentiation of gonad - (testis or ovary) late embryo, defining event in sexual differentiation
  3. Differentiation of internal genital organs and ducts - late embryo to fetal
  4. Differentiation of external genitalia - fetal
  5. Development of secondary sexual characteristics - puberty
Stage 22 mesonephros

Urogenital Indifferent Urogenital Male Urogenital Female

Human Timeline

  • Week 3-4 - primordial germ cells migrate during gastrulation
  • Week 4 - (24 days) intermediate mesoderm, pronephros primordium
  • Week 5 - (28 days) mesonephros and mesonephric duct
  • Week 6 - (35 days) ureteric bud, metanephros, genital ridge
  • Week 7 - (42 days) cloacal divison, gonadal primordium - indifferent to first appearance of testis cords
  • Week 8 - (49 days) paramesonephric duct, clear gonadal differentiation
  • Week 9 - (56 days) paramesonephric duct fusion (female)
  • Week 15 - (100 days) primary follicles (ovary)
Amnion 001 icon.jpg

1. Development of the indifferent gonad

  • intermediate mesoderm - (between somites and lateral plate mesoderm) kidneys and genital ridge develop.
  • kidney multiple stages - occur in a rostrocaudal sequence
    • pronephros > mesonephros > metanephros (true adult kidney)
  • pronephros (week 4) earliest structure to form featuring a pronephric duct with associated nephrogenic mesenchyme.
    • pronephros degenerates - leaving only the duct system running down to the cloaca (mesonephric duct = Wolffian duct).
  • mesonephros - next stage a series of mesonephric tubules in the mesenchyme that are induced by the mesonephric duct.
    • mesonephros degenerates - in mammals (In fish and amphibians it is the functioning adult kidney).
    • In mammals it serves mainly as the site for gonadal development.
Mesoderm-cartoon4.jpg

Urogenital sinus 001 icon.jpg Adrenal and gonad early development.jpg

Gonad and adrenal early development (not required to know molecular information)

2. Differentiation of gonad into testis or ovary

Chromosomal Sex Determination

Males Females
Y Chromosome
  • 59 million base pairs, hypervariable in length, mostly non-functional repeats
  • Current known protein-coding genes = 48 including SRY
  • SRY encodes a 204 amino acid protein (TDF) that is a member of the HMG (High mobility group) box class of DNA-binding proteins. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes.
X Chromosome
  • 155 million base pairs, contains about 5% of the haploid genome and encodes house-keeping and specialized functions.
  • Genes such as Wnt-4 and DAX-1 necessary for initiation of female pathway ovary development
Human Y chromosome SRY region.jpg Human X chromosome.jpg
X inactivation
  • one X chromosome randomly inactivated throughout the female embryo.
  • mosaic of maternal and paternally derived X chromosome activity in all tissues and organs.
Links: MBoC - Figure 20-18. Influence of Sry on gonad development | image (image provides a good overview of the anatomy of sex determination, I will refer to this in the lecture and practical class)

Supporting Cells

  • So called because they "support" the germ cells
Males Females
Sertoli cells
  • SRY is expressed in the primordia of the supporting cells, transforming them into Sertoli cells that surround the germ cells and form testis cords
    • SRY is not expressed in the other cell types of the gonad
  • Sertoli cells instruct the germ cells and the steroid secreting cells to take the male path of development
Granulosa cells
  • Follicle cells surround and nurture the developing oocytes
Seminiferous-tubule-HEx40.jpg Ovary follicle 01.jpg
  • embryonic cells - secrete anti-Mullerian hormone (AMH)
  • adult cells - line the inside of the seminiferous tubules and support spermatogenesis.
  • adult cells - in response to FSH, follicle cells proliferate
    • After ovulation, these cells become luteal cells of the corpus luteum secreting progesterone and estrogen

Steroid secreting cell lineage

Males Females
Leydig cells
  • (interstitial cells) that sit outside the seminiferous tubules
  • Secrete testosterone in response to luteinizing hormone from the pituitary
Theca cells
  • that sit outside the follicle granulosa cells
  • Secrete androstenedione that can be converted by the follicle cells into estrogens
Testis histology 2.jpg Ova20he.jpg

Primordial Germ Cells

Primordial germ cell region (Stage 9)
Genital Ridge (Stage 13)
  • Primordial germ cells (PGCs) are thought to be the first population of cells to migrate through the primitive streak in early gastrulation (week 3)
  • cells then lie at the hindgut yolk sac junctional region
  • later migrate into the genital ridge (germinal ridge) in early embryonic development.
Mouse Primordial Germ Cell Migration
Primordial germ cell 001 icon.jpg
 ‎‎Germ Cell E9.0
Page | Play
Primordial germ cell 002 icon.jpg
 ‎‎Germ Cell E9.5
Page | Play
Primordial germ cell 003 icon.jpg
 ‎‎Germ Cell E10.5
Page | Play
  • Not the primordial germ cells which respond to SRY presence or absence, but the supporting cells within the developing gonad.
    • Germ cells occasionally migrate by mistake into the developing adrenal gland and in the absence of sertoli cells telling them what to do, abnormally begin to develop as oocytes, even in males
Links: Germ cell migration pathway

Gametogenesis

  • forming PGCs as a small population of migratory cells
  • enter the gonad where they undergo several rounds of mitotic cell division
  • female - the germ cells enter meiosis and become arrested at the dictyate (diplotene) stage of meiotic prophase 1. All oocytes are at this stage at birth
  • male - the germ cells are enclosed by the developing Sertoli cells and are induced to arrest differentiation and cell division as T1 prospermatogonia until after birth.
Links: Image - Spermatogenesis | Image -Oogenesis

3. Differentiation of internal genital organs and ducts

Stage 22 Urogenital 1l.jpg

Human embryo (Carnegie stage 22, week 8) pelvic level cross-section.

Male

This looped animation shows the development of the male gonad showing medullary sex cords.
  • The paramesonephric duct (red, left) degenerates under the influence of anti-Mullerian hormone (AMH) secreted by sertoli cells.
  • The mesonephric duct (purple) is maintained and differentiates under the influence of Testosterone secreted by Leydig cells. Within the testes these mesonephric tubules grow towards the testis cords and will form the rete testis. The mesonephric duct extending out of the gonad forms the ductus deferens.
  • The testis cords (orange) containing the Sertoli cells and the germ cells (which are arrested as T1 prospermatogonia until after birth) later differentiate into seminiferous tubules which become hollow and actively produce spermatazoa during puberty.

The tunica albuginea (white) covers the testis and bands extend inward to form connective tissue septa.

Gonad-icon.jpg
 ‎‎Testis
Page | Play

Anti-Mullerian Hormone

Anti-Mullerian hormone (AMH) or Mullerian Inhibiting Substance (MIS) hormone with at least two gonadal related functions:

  • In males, it is produced by embryonic Sertoli cells and causes the loss of the paramesonephric (Mullerian) duct system that forms the internal female genital tract.
  • In females, it is produced after puberty by follicle cells and suppresses the development of other primary follicles, thus restricting the number of follicles stimulated by FSH.

Female

This looped animation shows the development of the female gonad showing cortical sex cords.
  • The mesonephric duct (purple) degenerates, small remnants may remain as epoophoron and paroophoron (in the mesentry of the ovary) and Gartner's cycts (near vagina).
  • The paramesonephric duct (red, left) grows forming the oviducts (fallopian tubes) and the end opens into the peritoneal cavity and terminates in fimbria (finger-like extensions). Away from the ovary, the two paramesonephric ducts fuse in the midline to form the uterus.
  • After entry of the germ cell into meiosis they are called oocytes and they are surrounded by the derivatives of the supporting cell lineage - the follicle cells or granulosa cells.
  • About 95% of the germ cells that entered meiosis in the female will be lost by a process called follicular atresia (see graph. Only about 400,000 remain at the time of puberty.

Infant ovary.jpg Human ovary non-growing follicle model.jpg

Gonad-icon.jpg
 ‎‎Ovary
Page | Play

Uterus Development

  • Week 7 – duct preservation or regression begins

Uterus 001 icon.jpg Paramesonephric duct.jpg Newborn uterus.jpg

Paramesonephric duct development

Vagina Development

  • The embryonic origin of the vagina has been a historically hotly debated issue with several different contributions and origins described.
  • Current molecular studies show the whole vagina is derived from the intermediate mesoderm-derived Müllerian duct (see review [1])
    • bone morphogenic protein 4 (BMP4) reshapes the duct into the vaginal primordium.
  • exhibits different features from the uterus
    • stratified squamous epithelium
    • insensitivity to anti-Müllerian hormone
Links: Vagina Development

4. Differentiation of External Genitalia

Historic diagram of external development

Endocrinology - Diagram of the development of the external genitalia | image

  • external genitalia are initially identical and undergo male and female differentiation under the influence or absence of steroidal sex hormones.
  • Indifferent stage ‐ cloaca divided by proliferating mesenchyme forming the urorectal septum which separates the ventral urogenital sinus from the dorsal rectum.
  • Difference stage ‐ locally in this region the presence or absence of dihydrotestosterone (DHT), generated from testosterone, determines male/female development.

Dihydrotestosterone (DHT)

Testosterone metabolism
  • Male presence of DHT
    • locally in this region leads to genital tubercle growth, form
    • genital folds (urethral) initial maintenance and then fusion, forming perineal and penile raphe.
    • labioscrotal swellings (lateral to urethreal folds) become the scrotum.
  • Female absence of DHT
    • genital tubercle remains small, bends caudally to form the clitoris.
    • genital folds (urethral) persist, do not fuse, and form labia minora.
    • open urogenital sinus forms a cleft into which urethra and vagina open.
    • labioscrotal swellings become the labia majora.

Female

Newborn uterus

This looped animation shows the development of external female genitalia from the indifferent external structure, covering the approximate period of week 9 to 12.

Urogenital septum 001 icon.jpg
 ‎‎Urogenital Septum
Page | Play
Female external 001 icon.jpg
 ‎‎Female External‎‎
Page | Play
Note the original cloacal membrane becomes separated into the urogenital membrane and anal membrane. The urogenital folds beneath the genital tubercle remain separate (unfused), forming the inner labia minora and second outer skin folds form the larger labia majora either side of the developing vestibule of the vagina. Note at the top of the animation, the changing relative size of the genital tubercle as it forms the glans of the clitoris.


Male Genitalia Development

Endocrinology - Box 6.6 The roles of testosterone (T) and 5α-dihydrotestosterone (DHT)

This looped animation shows the development of external male genitalia from the indifferent external structure, covering the approximate period of week 9 to 12.


Male external 001 icon.jpg
 ‎‎Male External
Page | Play

Note the original cloacal membrane becomes separated into the urogenital membrane and anal membrane (identical to female). The urogenital folds beneath the genital tubercle begin to fuse in the midline. The skin folds either side for the scrotum, which too has a midline fusion, the raphe. The scrotal sac is initially empty and is an attachment site for the gubernaculum, descent of the testes begins generally during week 26 and may take several days.

Gonad Descent

  • Both kidney and gonads develop retroperitoneally, with the gonads moving into the abdomen or eventually into the scrotal sacs.
  • During fetal development the gubernaculum and fetal growth in both male and female, changes the gonads’ relative positions finally reaching their adult locations.

Both female and male gonads undergo anatomical descent.

  • Ovaries ‐ undergo caudal and lateral shifts to be suspended in the broad ligament of the uterus, gubernaculum does not shorten, it attaches to paramesonephric ducts, causing medial movement into the pelvis.
  • Testes ‐ two anatomical phases in descent, transabdominal and transinguinal, under the influence of the shortening gubernaculum.
Testis 001 icon.jpg
 ‎‎Testis Descent
Page | Play
Testis-descent start.jpg Testis-descent end.jpg

The testis (white) lies in the subserous fascia (spotted) a cavity processus vaginalis evaginates into the scrotum, and the gubernaculum (green) attached to the testis shortens drawing it into the scrotal sac. As it descends it passes through the inguinal canal which extends from the deep ring (transversalis fascia) to the superficial ring (external oblique muscle). Descent of the testes into the scrotal sac begins generally during week 26 and may take several days. The animation shows the path of a single testis.

Data from a recent study of male human fetal (between 10 and 35 weeks) gonad position.

  • 10 to 23 weeks - (9.45%) had migrated from the abdomen and were situated in the inguinal canal
  • 24 to 26 weeks - (57.9%) had migrated from the abdomen
  • 27 to 29 weeks - (16.7%) had not descended to the scrotum

Incomplete or failed descent can occur unilaterally or bilaterally, is more common in premature births, and can be completed postnatally.

5. Postnatal - Puberty

Puberty growth

Puberty can occur over a broad range of time and differently for each sex:

  • girls (age 7 to 13)
  • boys (age 9 to 15)

The physical characteristics that can be generally measured are: genital stage, pubic hair, axillary hair, menarche, breast, voice change and facial hair.

Male

  • Testosterone - adult testes produce about 6-10 mg /day in males (~0.5 mg / day in females) carried in circulation by a specific carrier globulin.
  • masculinizing androgen - also at puberty, spermatogenesis in males
  • development of secondary sexual characteristics - body and facial hair growth (male pattern baldness)
  • anabolic effect - metabolism towards conservation of amino acids, promoting protein synthesis, muscle development
  • neural - libido in both sexes, male pattern behaviour
  • Sustentacular (Sertoli) cells - produce anti-mullerian hormone (AMH) to puberty.
    • AMH - anti-Müllerian hormone (Müllerian inhibiting factor (MIF), Müllerian-inhibiting hormone (MIH), and Müllerian-inhibiting substance (MIS)).

Male testosterone and AMH level graph.jpg

Female

Female HPG Axis

In females, menarche (the first menstruation or a period) usually occurs after the other secondary sex characteristics, and will continue until menopause (permanent cessation of reproductive fertility).

The diagram shows the hormonal regulation pathway from the brain to the ovary and subsequent impact on uterine changes during the menstral cycle.

  • GnRH = Gonadotropin-releasing hormone (GnRH). This peptide hormone is a decapeptide (10 amino acids) with a short half life (<15 minutes).
  • LH = Luteinizing Hormone
  • FSH = Follicle Stimulating Hormone

A similar endocrine axis is also found for regulation of the male gonad.

Puberty Abnormalities

  • Precocious Puberty - Premature development of the signs of puberty which can occur in both girls (before age 7 or 8) and in boys (before age 9).
  • Delayed Puberty - Determined in boys by a lack of increase in testicular volume by the age of 14 years. In girls, no breast development by the age of 13.5 years and a lack of menstruation by the age of 16 years. There can also be a "pubertal arrest" where there is no progress in puberty over 2 year period.

Sex Differences in Adult and Developing Brains

Brains of males and females differ

  • in regions specialized for reproduction
  • in other regions (controlling cognition, etc) where sex differences are not necessarily expected
  • differentially susceptible to neurological and psychiatric disease

2 sources of sexually dimorphic information

  • complement of sex chromosome genes
  • mix of gonadal hormones
  • not known significance of brain sex differences
  • transient sex differences in gene expression in developing brains may cause permanent differences in brain structure

Abnormalities

Human genital abnormalities are currently described as "Disorders of Sex Development" (DSD).

Include: chromosomal, gonadal dysfunction, tract abnormalities, external genitalia and gonadal descent.

Sex Reversal

  • Where chromosomal sex does not match phenotypic sex i.e. XX males or XY females.

XX males - usually caused by a transfer of some Y chromosome DNA onto the X chromosome

  • Gonads develop as testes, everything looks normal internally and externally but infertile due to a failure of spermatogenesis
  • Similar to Kleinfelters syndrome (XXY)

XY females - usually steroidal origin

  • Main cause is Androgen Insensitivity Syndrome (AIS) Complete (CAIS) Partial (PAIS) and Mild (MAIS) usually caused by mutations of the gene encoding the androgen receptor AR gene located on the X chromosome
  • 5-alpha-reductase deficiency - again leads to a lack of complete steroidal induction of external genitalia
  • Rare mutations in key sex determining genes including deletion or mutations of SRY


Links: Genital System - Abnormalities

Congenital Adrenal Hyperplasia

  • impairment of cortisol production by the adrenal cortex, is one of the most common causes of intersex genitalia at birth.
  • genetically male (XY) infants born with undervirilized genitalia are often assigned and reared as girls.

Cryptorchidism

Cryptorchidism
  • abnormality of either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males.
  • Descent may complete postnatally in the first year, failure to descend can result in sterility.

Testis descent is thought to have 2 phases:

  1. transabdominal descent - dependent on insulin-like hormone 3 (INSL3).
  2. inguinoscrotal descent - dependent on androgens.

Undescended Ovaries

  • reasonably rare gonad abnormality, often detected following clinical assessment of fertility problems and may also be associated with other uterine malformations (unicornuate uterus).
  • Due to the relative positions of the male (external) and female (internal) gonads and the pathways for their movement, failure of gonad descent is more apparent and common in male cryptorchidism than female undescended ovaries.

Hydrocele

  • Male Hydrocele is a fluid-filled cavity of either testis or spermatic cord, where peritoneal fluid passes into a patent processus vaginalis.
  • Female Hydrocele is a similar, but rarer, fluid-filled cavity occuring in the female as a pouch of peritoneum extending into the labium majorum (canal of Nuck).

Tract Abnormalities

Many different forms

  • Uterine: associated with other anomolies, unicornuate uterus
  • Vagina: agenesis, atresia
  • Ductus Deferens: Unilateral or bilateral absence, failure of mesonephric duct to differentiate
Uterine abnormalities.jpg Unicornate uterus
Uterine abnormalities Unicornate uterus

Uterine Duplication (uterus didelphys, double uterus, uterus didelphis) A rare uterine developmental abnormality where the paramesonephric ducts (Mullerian ducts) completely fail to fuse generating two separate uterus parts each connected to the cervix and having an ovary each.

Septate Uterus

Cervical: cervical agenesis, cervical duplication

Vaginal: Mayer-Rokitansky syndrome (MRK anomaly, Rokitansky-Küster-Hauser syndrome, RKH syndrome, RKH) congenital absence of the vagina, dyspareunia, vaginal agenesis.

External Genitalia - Hypospadia

  • most common penis abnormality (1 in 300) from a failure of male urogenital folds to fuse in various regions and resulting in a proximally displaced urethral meatus.
  • The cause is unknown, but suggested to involve many factors either indivdually or in combination including: familial inheritance, low birth weight, assisted reproductive technology, advanced maternal age, paternal subfertility and endocrine-disrupting chemicals. Infants with hypospadias should not undergo circumcision.
Hypospadia classifications.jpg

Hypospadia classifications

Movies

Gonad-icon.jpg
 ‎‎Ovary
Page | Play
Gonad-icon.jpg
 ‎‎Testis
Page | Play
Urogenital septum 001 icon.jpg
 ‎‎Urogenital Septum
Page | Play
Female external 001 icon.jpg
 ‎‎Female External‎‎
Page | Play
Male external 001 icon.jpg
 ‎‎Male External
Page | Play
Uterus 001 icon.jpg
 ‎‎Uterus
Page | Play
Testis 001 icon.jpg
 ‎‎Testis Descent
Page | Play
Gonad blood 01 icon.jpg
 ‎‎Gonad Vascular
Page | Play
Mouse Primordial Germ Cell Migration
Primordial germ cell 001 icon.jpg
 ‎‎Germ Cell E9.0
Page | Play
Primordial germ cell 002 icon.jpg
 ‎‎Germ Cell E9.5
Page | Play
Primordial germ cell 003 icon.jpg
 ‎‎Germ Cell E10.5
Page | Play

References

  1. <pubmed>19598112</pubmed>

Textbooks

  • Before We Are Born (5th ed.) Moore and Persaud Chapter 14 p289-326
  • Essentials of Human Embryology, Larson Chapter 10 p173-205
  • Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 p134-152

Online Textbooks

Reviews

<pubmed>17237341</pubmed>| Physiol. Rev. | Figure Links

Search

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.


 2017 ANAT2341 - Timetable | Course Outline | Group Projects | Moodle | Tutorial 1 | Tutorial 2 | Tutorial 3

Labs: 1 Fertility and IVF | 2 ES Cells to Genome Editing | 3 Preimplantation and Early Implantation | 4 Reproductive Technology Revolution | 5 Cardiac and Vascular Development | 6 CRISPR-Cas9 | 7 Somitogenesis and Vertebral Malformation | 8 Organogenesis | 9 Genetic Disorders | 10 Melanocytes | 11 Stem Cells | 12 Group

Lectures: 1 Introduction | 2 Fertilization | 3 Week 1/2 | 4 Week 3 | 5 Ectoderm | 6 Placenta | 7 Mesoderm | 8 Endoderm | 9 Research Technology | 10 Cardiovascular | 11 Respiratory | 12 Neural crest | 13 Head | 14 Musculoskeletal | 15 Limb | 16 Renal | 17 Genital | 18 Endocrine | 19 Sensory | 20 Fetal | 21 Integumentary | 22 Birth | 23 Stem cells | 24 Revision

 Student Projects: 1 Cortex | 2 Kidney | 3 Heart | 4 Eye | 5 Lung | 6 Cerebellum