Genital - Female 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 initially makes the "difference". The paramesonephric (Müllerian Duct) contribute the majority of female internal genital tract, while the mesonephric duct degenerates.


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.


There are also currently separate pages describing Ovary Development | Oocyte Development | Uterus Development | Vagina Development | Menstrual Cycle | X Inactivation


Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital
Female | X | X inactivation | ovary | corpus luteum | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Category:Female
Male | Y | SRY | testis | spermatozoa | ductus deferens | penis | prostate | Category:Male
Historic Embryology - Genital 
General: 1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1921 Urogenital Development | 1921 External Genital | 1942 Sex Cords | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer
Female: 1904 Ovary and Testis | 1904 Hymen | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1921 External Genital | 1927 Female Foetus 15 cm | 1927 Vagina | 1932 Postnatal Ovary
Male: 1887-88 Testis | 1904 Ovary and Testis | 1904 Leydig Cells | 1906 Testis vascular | 1909 Prostate | 1912 Prostate | 1914 External Genitalia | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | Historic Embryology Papers | Historic Disclaimer

Some Recent Findings

Male urogenital development (stage 22)
  • FOXL2 is a female sex-determining gene in the goat[1] "The origin of sex reversal in XX goats homozygous for the polled intersex syndrome (PIS) mutation was unclear because of the complexity of the mutation that affects the transcription of both FOXL2 and several long noncoding RNAs (lncRNAs). Accumulating evidence suggested that FOXL2 could be the sole gene of the PIS locus responsible for XX sex reversal, the lncRNAs being involved in transcriptional regulation of FOXL2. In this study, using zinc-finger nuclease-directed mutagenesis, we generated several fetuses, of which one XX individual bears biallelic mutations of FOXL2. Our analysis demonstrates that FOXL2 loss of function dissociated from loss of lncRNA expression is sufficient to cause an XX female-to-male sex reversal in the goat model and, as in the mouse model, an agenesis of eyelids. Both developmental defects were reproduced in two newborn animals cloned from the XX FOXL2(-/-) fibroblasts. These results therefore identify FOXL2 as a bona fide female sex-determining gene in the goat. They also highlight a stage-dependent role of FOXL2 in the ovary, different between goats and mice, being important for fetal development in the former but for postnatal maintenance in the latter.
  • Temporal and spatial dissection of Shh signaling in genital tubercle development.[2] "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. [3] "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
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Search term: female sex-determining

<pubmed limit=5>female sex-determining</pubmed>

Textbooks

Historic drawing of the ovary
  • 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

Movies

Urogenital sinus 001 icon.jpg Urogenital septum 001 icon.jpg
Urogenital Sinus Urogenital Septum
Uterus 001 icon.jpg Female external 001 icon.jpg
Uterus Female External


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)

Gonad - Ovary

Primordial germ cell migration (mouse)

Primordial germ cell 001 icon.jpg Primordial germ cell 002 icon.jpg Primordial germ cell 003 icon.jpg
Migration 1 Migration 2 Migration 3


Links: Ovary Development | Puberty Development

Internal Genital

Historic Images of Genital Changes

Urogenital Indifferent Urogenital Female
Urogenital indifferent Urogenital female

Fetal Week 10

Planes of fetal sections
Fetal 10wk urogenital 1.jpg Fetal 10wk urogenital 2.jpg
Ovary Ovary
Fetal 10wk urogenital 3.jpg Fetal 10wk urogenital 4.jpg
Uterus Uterus


Links: Uterus Development | Vagina Development | Female Fetal Week 10

External Genital

These images are from a 1921 historic paper[4] describing embryonic to metal development of human external genitalia.

Links: 1921 article

Molecular

Y and X Chromosomes
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.

Ovary - Notum, Phlda2, Runx-1 and Msx1 genes

DAX-1

Wnt-4

First identified in 1999 as a female specific gene[5], it has been recently shown to be an upstream regulator of Runx-1 expression.[6]


References

  1. <pubmed>24485832</pubmed>
  2. <pubmed>19906863</pubmed>
  3. <pubmed>19159697</pubmed>
  4. Spaulding, M.H., The development of the external genitalia in the human embryo. Contributions to Embryology Carnegie Institution No.61 (1921). With four plates and two text-figures.
  5. <pubmed>9989404</pubmed>| Nature
  6. <pubmed>25645944</pubmed>| Exp Cell Res.


Reviews

<pubmed>20846260</pubmed> <pubmed>19597684</pubmed> <pubmed></pubmed>

Articles

<pubmed></pubmed> <pubmed></pubmed> <pubmed>12740945</pubmed> <pubmed></pubmed>

Search PubMed

Search Pubmed: Female Genital System Development | paramesonephric duct development | paramesonephric duct

Additional Images

Terms

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Cite this page: Hill, M.A. (2024, March 28) Embryology Genital - Female Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_-_Female_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G