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 | 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 | 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)
  • 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
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: female sex-determining

Tong-Chun Xue, Sheng-Long Ye Reply. Dig. Dis. Sci.: 2015, 60(4);1111-2 PMID: 26086060 José F Pérez-Gutiérrez, Luís V Monteagudo, Antonio Rodríguez-Bertos, Enrique García-Pérez, María J Sánchez-Calabuig, Concepción García-Botey, Ana Whyte, Mercedes Sánchez de la Muela Bilateral Ovotestes in a 78, XX SRY-Negative Beagle Dog. J Am Anim Hosp Assoc: 2015; PMID: 26083441 Xiaofang Jiang, James K Biedler, Yumin Qi, Andrew Brantley Hall, Zhijian Jake Tu Complete dosage compensation in Anopheles stephensi and the evolution of sex-biased genes in mosquitoes. Genome Biol Evol: 2015; PMID: 26078263 Deborah Charlesworth Plant contributions to our understanding of sex chromosome evolution. New Phytol.: 2015; PMID: 26053356 Chuan-Liang Deng, Ning-Na Wang, Shu-Fen Li, Tian-Yu Dong, Xin-Peng Zhao, Shao-Jing Wang, Wu-Jun Gao, Long-Dou Lu Isolation of differentially expressed sex genes in garden asparagus using suppression subtractive hybridization. J. Plant Res.: 2015; PMID: 26038270

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


Molecular

  • 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.


Dax-1

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

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. 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 PMID: 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 PMID: 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 PMID: 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 PMID: 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 PMID: 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; PMID: 25645944 | Exp Cell Res.


Reviews

Yasmin Sajjad Development of the genital ducts and external genitalia in the early human embryo. J. Obstet. Gynaecol. Res.: 2010, 36(5);929-37 PMID: 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 PMID: 19597684


Articles

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 PMID: 12740945

Search PubMed

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

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Cite this page: Hill, M.A. (2015) Embryology Genital - Female Development. Retrieved July 4, 2015, from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_-_Female_Development

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© Dr Mark Hill 2015, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G