Genital - Female Development

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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 | X chromosome | Trisomy X

Genital Links: Introduction | Lecture - Medicine | Lecture - Science | Medicine - Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Reproductive Cycles | Menstrual Cycle | Male | Testis | Spermatozoa | Penis | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
Historic Embryology - Genital 
1902 The Uro-Genital System | 1912 Urinogenital Organ Development | 1915 Cowper’s and Bartholin’s Glands | 1921 Urogenital Development | 1921 External Genital Development | 1927 Female Foetus 15 cm | 1932| Postnatal Ovary | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | 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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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 | Journal Searches

Search term: female sex-determining

Yuning Song, Tingjun Liu, Yong Wang, Jichao Deng, Mao Chen, Lin Yuan, Yi Lu, Yuxin Xu, Haobin Yao, Zhanjun Li, Liangxue Lai Mutation of the Sp1 binding site in the 5' flanking region of SRY causes sex reversal in rabbits. Oncotarget: 2017; PubMed 28445127

Mikako Wada, Kazuko Fujitani, Kei Tamura, Shuuji Mawaribuchi, Yosuke Kamata, Nobuhiko Takamatsu, Michihiko Ito Masculinization-Related Genes and Cell-Mass Structures During Early Gonadal Differentiation in the African Clawed Frog Xenopus laevis. Zool. Sci.: 2017, 34(2);105-111 PubMed 28397603

Ilona Hromadnikova, Katerina Kotlabova, Ladislav Krofta, Filip Hron Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated RASSF1A, and SRY sequences. Tumour Biol.: 2017, 39(4);1010428317697548 PubMed 28381180

Yur-Ren Kuo, Chien-Chang Chen, Yen-Chou Chen, Ching-Ming Chien Recipient Adipose-derived Stem Cells Enhance Recipient Cell Engraftment and Prolong Allotransplant Survival in a Miniature Swine Hind-limb Model. Cell Transplant: 2017; PubMed 28379122

Mohammad Amin Almasi, Galavizh Almasi Loop Mediated Isothermal Amplification (LAMP) for Embryo Sex Determination in Pregnant Women at Eight Weeks of Pregnancy. J Reprod Infertil: 2017, 18(1);197-204 PubMed 28377900


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


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


  • Paramesonephric duct - Wnt-7a Pax-8 expression associated with the initial stages of paramesonephric duct development
  • Ovary - Notum, Phlda2, Runx-1 and Msx1 genes
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.


DAX1 (NR0B1) is a nuclear receptor with a characteristic C-terminal ligand binding domain, but an atypical DNA binding domain, for review see[4] DAX1 protein is localized mainly in the nucleus and can bind to an RA responsive element (RARE).

Links: OMIM 300473


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]


  1. Laurent Boulanger, Maëlle Pannetier, Laurence Gall, Aurélie Allais-Bonnet, Maëva Elzaiat, Daniel Le Bourhis, Nathalie Daniel, Christophe Richard, Corinne Cotinot, Norbert B Ghyselinck, Eric Pailhoux FOXL2 is a female sex-determining gene in the goat. Curr. Biol.: 2014, 24(4);404-8 PubMed 24485832
  2. 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 PubMed 19906863
  3. 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 PubMed 19159697
  4. Edward R B McCabe DAX1: Increasing complexity in the roles of this novel nuclear receptor. Mol. Cell. Endocrinol.: 2007, 265-266;179-82 PubMed 17210221 | PMC1847396/
  5. S Vainio, M Heikkilä, A Kispert, N Chin, A P McMahon Female development in mammals is regulated by Wnt-4 signalling. Nature: 1999, 397(6718);405-9 PubMed 9989404 | Nature
  6. Florence Naillat, Wenying Yan, Riikka Karjalainen, Anna Liakhovitskaia, Anatoly Samoylenko, Qi Xu, Zhandong Sun, Bairong Shen, Alexander Medvinsky, Susan Quaggin, Seppo J Vainio Identification of the Genes regulated by Wnt-4, a critical signal for commitment of the ovary. Exp. Cell Res.: 2015; PubMed 25645944 | Exp Cell Res.


Yasmin Sajjad Development of the genital ducts and external genitalia in the early human embryo. J. Obstet. Gynaecol. Res.: 2010, 36(5);929-37 PubMed 20846260

Sérgio Conti Ribeiro, Renata Assef Tormena, Thais Villela Peterson, Marina de Oliveira Gonzáles, Priscila Gonçalves Serrano, José Alcione Macedo de Almeida, Edmund Chada Baracat Müllerian duct anomalies: review of current management. Sao Paulo Med J: 2009, 127(2);92-6 PubMed 19597684


Ryozo Hashimoto Development of the human Müllerian duct in the sexually undifferentiated stage. Anat Rec A Discov Mol Cell Evol Biol: 2003, 272(2);514-9 PubMed 12740945

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

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Cite this page: Hill, M.A. 2017 Embryology Genital - Female Development. Retrieved April 27, 2017, from

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G