Genital System Development

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Introduction

Female uterus development

The male and female reproductive systems develop initially "indifferently", it is the product of the Y chromosome SRY gene that makes the "difference". Mesonephric duct (Wolffian Duct) and paramesonephric (Müllerian 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.

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.


This current page provides only a general introduction to the topic, use the links listed below to read about specific developmental topics.


Genital Links: Introduction | Lecture - Medicine | Lecture - Science | Online Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Reproductive Cycles | Menstrual Cycle | Male | Testis | Spermatozoa | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
Historic Embryology - Genital
1902 The Uro-Genital System | 1912 Urinogenital Organ Development | 1921 Urogenital Development | 1921 External Genital Development | Historic Disclaimer

Some Recent Findings

Male urogenital development (stage 22)
  • Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination[1] "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."
  • Male reproductive tract abnormalities: More common after assisted reproduction?[2] "IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias."
  • Temporal and spatial dissection of Shh signaling in genital tubercle development.[3] "Genital tubercle (GT) initiation and outgrowth involve coordinated morphogenesis of surface ectoderm, cloacal mesoderm and hindgut endoderm. GT development appears to mirror that of the limb. Although Shh is essential for the development of both appendages, its role in GT development is much less clear than in the limb. Here, by removing Shh at different stages during GT development in mice, we demonstrate a continuous requirement for Shh in GT initiation and subsequent androgen-independent GT growth."
  • Bmp7 expression and null phenotype in the urogenital system suggest a role in re-organization of the urethral epithelium. [4] "Signaling by Bone morphogenetic proteins (Bmps) has multiple and diverse roles in patterning and morphogenesis of the kidney, eye, limbs and the neural tube. ...Together, our analysis of Bmp7 expression and the null phenotype, indicates that Bmp7 may play an important role in re-organization of the epithelium during cloacal septation and morphogenesis of the genital tubercle."
More recent papers
Mark Hill.jpg
This table shows an automated computer PubMed search using the listed sub-heading term.
  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent


Search term: Genital Embryology

Satomi S Tanaka, Ryuichi Nishinakamura Regulation of male sex determination: genital ridge formation and Sry activation in mice. Cell. Mol. Life Sci.: 2014; PMID:25139092 W A A Tjalma Abdominal intrauterine vacuum aspiration. Clin Exp Obstet Gynecol: 2014, 41(4);462-4 PMID:25134300 Keiko Horioka, Keiko Kataoka, Hiroko Ooishi, Ryousuke Tsunematsu, Kaoru Okugawa, Hiroaki Kobayashi, Kiyoko Kato [Case of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome]. Fukuoka Igaku Zasshi: 2014, 105(3);84-7 PMID:25000661 Ahmed T Hadidi, Jasmin Roessler, Wiltrud Coerdt Development of the human male urethra: A histochemical study on human embryos. J. Pediatr. Surg.: 2014, 49(7);1146-52 PMID:24952805 László Ságodi, Akos Kiss, Emőke Kiss-Tóth, László Barkai [Prevalence and possible causes of hypospadias]. [A hypospadiasis gyakorisága és lehetséges okai.] Orv Hetil: 2014, 155(25);978-85 PMID:24936573

Textbooks

  • Human Embryology (2nd ed.) Larson Chapter 10 p261-306
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 13 p303-346
  • 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
  • Developmental Biology (6th ed.) Gilbert Chapter 14 Intermediate Mesoderm
UNSW Students
Mark Hill.jpg You have access the following online Embryology textbooks through the UNSW Library.
The Developing Human, 8th edn.jpg Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders.
Larsen's human embryology 4th edn.jpg Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4th ed.). New York; Edinburgh: Churchill Livingstone.

Historic-ovary.jpg Historic-testis.jpg

Objectives

  • 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.

Movies

Gonad-icon.jpg
 ‎‎Ovary
Page | Play
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
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
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Primordial germ cell 003 icon.jpg
 ‎‎Germ Cell E10.5
Page | Play

Development Overview

Three main stages during development, 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.

  1. Differentiation of gonad (Sex determination)
  2. Differentiation of internal genital organs
  3. 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? Puberty Development)

Sexual Development Genes

Table below modified from Table 1. Genes implicated in sexual development in mammals in recent review article.[5]

Gene Protein Function Gonad Phenotype of Null Mice Human Syndrome
Bipotential gonad
Wt1 Transcription factor Blockage in genital ridge development Denys-Drash, WAGR, Frasier syndrome
Sf1 Nuclear receptor Blockage in genital ridge development Embryonic testicular regression syndrome
Lhx9 Transcription factor Blockage in genital ridge development a
Emx2 Transcription factor Blockage in genital ridge development a
M33 Transcription factor Gonadal dysgenesis a
Testis-determining pathway
Gata4/Fog2 Transcription/cofactor Reduced Sry levels, XY sex reversal a
Sry Transcription factor XY sex reversal XY sex reversal (LOF); XX sex reversal (GOF)
Sox9 Transcription factor XY sex reversal Campomelic dysplasia, XX sex reversal (GOF)
Sox8 Transcription factor XY sex reversal in combination with partial loss of Sox9 function a
Fgf9 Signaling molecule XY sex reversal a
Dax1 Nuclear receptor Impaired testis cord formation and spermatogenesis Hypogonadism
Pod1 Transcription factor XY sex reversal a
Dhh Signaling molecule Impaired differentiation of Leydig and PM cells XY gonadal dysgenesis
Pgdra Receptor Reduction in mesonephric cell migration a
Pgds Enzyme No phenotype a
Arx Transcription factor Abnormal testicular differentiation X-linked lissencephaly with abnormal genitalia
Atrx Helicase ND ATRX syndrome
Insl3 Signaling factor Blockage of testicular descent Cryptorchidism
Lgr8 Receptor Blockage of testicular descent Cryptorchidism
Hoxa10 Transcription factor Blockage of testicular descent Cryptorchidism
Hoxal1 Transcription factor Blockage of testicular descent Cryptorchidism
Amh Hormone No Müllerian duct degeneration Persistent Müllerian duct syndrome
Misrl1 Receptor No Müllerian duct degeneration Persistent Müllerian duct syndrome
Pax2 Transcription factor Dysgenesis of mesonephric tubules a
Lim1 Transcription factor Agenesis of Wolffian and Müllerian ducts a
Dmrt1 Transcription factor Loss of Sertoli and germ cells XY femaleb
Ovary-determining pathway
Wnt4 Signaling molecule Müllerian duct agenesis, testosterone synthesis, and coelomic vessel formation XY female (GOF)
FoxL2 Transcription factor Premature ovarian failure BPES
Dax1 Nuclear receptor XY sex reversal (GOF) XY sex reversal (GOF)

  • BPES - blepharophimosis-ptosis-epicanthus inversus syndrome
  • GOF - gain-of-function mutation
  • LOF - loss-of-function mutation
  • ND - not determined
  • WAGR - Wilms' tumor-aniridia-genitourinary malformations-mental retardation

a No mutations in human sexual disorders identified to date.

b Candidate gene for 9p deletion, XY sex reversal.

Historic

See also section Historic Embryology Images.

Johannes Müller (1801-1858)


Historic Images of Genital Changes

Urogenital Indifferent Urogenital Male Urogenital Female
Urogenital indifferent Urogenital male Urogenital female

Additional Images

Historic Embryology Images

Historic Disclaimer - information about historic embryology pages
Mark Hill.jpg
Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding. (More? Embryology History)

Keith, A. (1902) Human Embryology and Morphology. London: Edward Arnold.

Chapter 9 - The Uro-genital System

The Uro-genital System: Fig. 79. Wolffian Body | Fig. 80. Wolffian and Genital Ridges | Fig. 81. Female Wolffian Body Remnants | Fig. 82. Male Wolffian Body Remnants |Fig. 83. Renal Bud | Fig. 84. Ureter in the Bladder | Fig. 85. Wolffian and Müllerian Ducts | Fig. 86. Genital Ducts 3rd month | Fig. 87. Müllerian Ducts 3rd month | Fig. 88. Uterus | Fig. 89. Uterus and Vagina | Fig. 90. Prostate remnants of Müllerian Ducts | Fig. 91. Prostate showing an unusual Uterus Masculinus | Fig. 92. Female Uro-genital Sinus | Fig. 93. Male Uro-genital Sinus | Fig. 94. Vagina and Uterus at 7th month | Fig. 95. Division of the Cloaca | Fig. 96. Imperforate Anus | Fig. 97. Cloacal Septum has failed to fuse with Perineal Septum | Fig. 98. The Uro-genital Cleft 2nd month | Fig. 99. Male bladder and urethra at birth | Fig. 100. Ectopia Vesicae | Fig. 101. Prostatic Tubules | Fig. 102. Testis in a foetus of 2£ months | Fig. 103. Testis at the 6th month | Fig. 104. Inguinal Canal and Coverings of the Testis | Fig. 105. Processus Vaginalis | Figures

References

  1. Steven C Munger, Anirudh Natarajan, Loren L Looger, Uwe Ohler, Blanche Capel Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination. PLoS Genet.: 2013, 9(7);e1003630 PMID:23874228
  2. Simone Funke, Edina Flach, István Kiss, János Sándor, Gabriella Vida, József Bódis, Tibor Ertl Male reproductive tract abnormalities: more common after assisted reproduction? Early Hum. Dev.: 2010, 86(9);547-50 PMID:20674196
  3. Congxing Lin, Yan Yin, G Michael Veith, Alexander V Fisher, Fanxin Long, Liang Ma Temporal and spatial dissection of Shh signaling in genital tubercle development. Development: 2009, 136(23);3959-67 PMID:19906863
  4. Xinyu Wu, Christopher Ferrara, Ellen Shapiro, Irina Grishina Bmp7 expression and null phenotype in the urogenital system suggest a role in re-organization of the urethral epithelium. Gene Expr. Patterns: 2009, 9(4);224-30 PMID:19159697
  5. Dagmar Wilhelm, Stephen Palmer, Peter Koopman Sex determination and gonadal development in mammals. Physiol. Rev.: 2007, 87(1);1-28 PMID:17237341 | Physiol. Rev.


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Cite this page: Hill, M.A. (2014) Embryology Genital System Development. Retrieved September 19, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Genital_System_Development

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© Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G