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.
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."
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More recent papers
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Search term: Genital Embryology
<pubmed limit=5>Genital Embryology</pubmed>
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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
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You have access the following online Embryology textbooks through the UNSW Library.
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Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders.
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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.
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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
Mouse Primordial Germ Cell Migration
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Mouse Primordial Germ Cell Migration
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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.
- Differentiation of gonad (Sex determination)
- Differentiation of internal genital organs
- Differentiation of external genital organs
The 2nd and 3rd stages dependent on endocrine gonad. Reproductive development has a long maturation timecourse, begining in the embryo and finishing in puberty. (More? Puberty Development)
Sexual Development Genes
Table below modified from Table 1. Genes implicated in sexual development in mammals in recent review article.[5]
Gene
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Protein Function
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Gonad Phenotype of Null Mice
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Human Syndrome
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Bipotential gonad
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Wt1
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Transcription factor
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Blockage in genital ridge development
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Denys-Drash, WAGR, Frasier syndrome
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Sf1
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Nuclear receptor
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Blockage in genital ridge development
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Embryonic testicular regression syndrome
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Lhx9
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Transcription factor
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Blockage in genital ridge development
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a
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Emx2
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Transcription factor
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Blockage in genital ridge development
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a
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M33
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Transcription factor
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Gonadal dysgenesis
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a
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Testis-determining pathway
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Gata4/Fog2
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Transcription/cofactor
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Reduced Sry levels, XY sex reversal
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a
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Sry
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Transcription factor
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XY sex reversal
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XY sex reversal (LOF); XX sex reversal (GOF)
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Sox9
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Transcription factor
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XY sex reversal
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Campomelic dysplasia, XX sex reversal (GOF)
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Sox8
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Transcription factor
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XY sex reversal in combination with partial loss of Sox9 function
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a
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Fgf9
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Signaling molecule
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XY sex reversal
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a
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Dax1
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Nuclear receptor
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Impaired testis cord formation and spermatogenesis
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Hypogonadism
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Pod1
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Transcription factor
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XY sex reversal
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a
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Dhh
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Signaling molecule
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Impaired differentiation of Leydig and PM cells
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XY gonadal dysgenesis
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Pgdra
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Receptor
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Reduction in mesonephric cell migration
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a
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Pgds
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Enzyme
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No phenotype
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a
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Arx
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Transcription factor
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Abnormal testicular differentiation
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X-linked lissencephaly with abnormal genitalia
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Atrx
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Helicase
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ND
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ATRX syndrome
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Insl3
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Signaling factor
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Blockage of testicular descent
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Cryptorchidism
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Lgr8
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Receptor
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Blockage of testicular descent
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Cryptorchidism
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Hoxa10
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Transcription factor
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Blockage of testicular descent
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Cryptorchidism
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Hoxal1
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Transcription factor
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Blockage of testicular descent
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Cryptorchidism
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Amh
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Hormone
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No Müllerian duct degeneration
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Persistent Müllerian duct syndrome
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Misrl1
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Receptor
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No Müllerian duct degeneration
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Persistent Müllerian duct syndrome
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Pax2
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Transcription factor
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Dysgenesis of mesonephric tubules
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a
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Lim1
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Transcription factor
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Agenesis of Wolffian and Müllerian ducts
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a
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Dmrt1
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Transcription factor
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Loss of Sertoli and germ cells
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XY femaleb
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Ovary-determining pathway
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Wnt4
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Signaling molecule
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Müllerian duct agenesis, testosterone synthesis, and coelomic vessel formation
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XY female (GOF)
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FoxL2
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Transcription factor
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Premature ovarian failure
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BPES
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Dax1
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Nuclear receptor
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XY sex reversal (GOF)
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XY sex reversal (GOF)
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- 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
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a No mutations in human sexual disorders identified to date.
b Candidate gene for 9p deletion, XY sex reversal.
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Historic
See also section Historic Embryology Images.
Johannes Müller (1801-1858)
Historic Images of Genital Changes
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Urogenital indifferent
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Urogenital male
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Urogenital female
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Additional Images
Rabbit Gonad Development Timeline PMID 23593221
Stages of primordial germ cell migration PMID 20027186
Historic Embryology Images
Historic Disclaimer - information about historic embryology pages
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Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, 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, interpretations and recommendations may not reflect our current scientific understanding. (More? Embryology History | Historic Embryology Papers)
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Historic - Showing the developing mesonephros.
Historic - Human embryo of 5 weeks genital ridge.
Historic - Persistent portions of the mesonephros in the male.
Historic - Persistent portions of the mesonephros in the female.
Historic - Section of testicle pig embryo of 62 mm.
Historic - external genitalia embryo 16.8 mm long.
Historic - external genitalia beginning of definitive period 45-49 mm.
Historic - embryo 9-15 mm.
Historic - embryo 14-25 mm.
Historic - embryo 37-51 mm.
Historic - embryo 51-100 mm.
References
- ↑ <pubmed>23874228 </pubmed>
- ↑ <pubmed>20674196</pubmed>
- ↑ <pubmed>19906863</pubmed>
- ↑ <pubmed>19159697</pubmed>
- ↑ <pubmed>17237341</pubmed>| Physiol. Rev.
Reviews
Articles
Search PubMed
Search April 2010
- Genital System Development - All (868) Review (212) Free Full Text (170)
- Genital Development - All (5365) Review (1170) Free Full Text (1024)
Search Pubmed: Genital System Development | Genital Development
Terms
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Cite this page: Hill, M.A. (2024, April 23) Embryology Genital System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_System_Development
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