Talk:Vagina Development

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

10 Most Recent Papers

Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)

Cervix Embryology

Lee A Richter, Elizabeth Coviello, Kelly Loftus, Robert E Gutman Uretero-Uterine Fistula: Delayed Presentation After Ureteral Reimplantation for Vesicoureteral Reflux. Female Pelvic Med Reconstr Surg: 2015; PMID: 25730434 Soha Siam, Badeea S Soliman Combined laparoscopy and hysteroscopy for the detection of female genital system anomalies results of 3,811 infertile women. J Reprod Med: 2015, 59(11-12);542-6 PMID: 25552125 A Ludwin, I Ludwin Comparison of the ESHRE-ESGE and ASRM classifications of Müllerian duct anomalies in everyday practice. Hum. Reprod.: 2014; PMID: 25534461 Armen Nersesyan, Michael Kundi, Michael Fenech, Claudia Bolognesi, Miroslav Misik, Georg Wultsch, Michaele Hartmann, Siegfried Knasmueller Micronucleus assay with urine derived cells (UDC): A review of its application in human studies investigating genotoxin exposure and bladder cancer risk. Mutat Res Rev Mutat Res: 2014, 762C;37-51 PMID: 25485594 Yiming Luo, Qian Yao, Caixia Ren, Xue Ding, Ajin Hu, Congrong Liu HPV infection status in cervical metaplastic carcinomas. J. Clin. Pathol.: 2014; PMID: 25452397

Vagina Embryology

Lee A Richter, Elizabeth Coviello, Kelly Loftus, Robert E Gutman Uretero-Uterine Fistula: Delayed Presentation After Ureteral Reimplantation for Vesicoureteral Reflux. Female Pelvic Med Reconstr Surg: 2015; PMID: 25730434 Stefano Salvatore, Umberto Leone Roberti Maggiore, Stavros Athanasiou, Massimo Origoni, Massimo Candiani, Alberto Calligaro, Nicola Zerbinati Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause: 2015; PMID: 25608269 A Ludwin, I Ludwin Comparison of the ESHRE-ESGE and ASRM classifications of Müllerian duct anomalies in everyday practice. Hum. Reprod.: 2014; PMID: 25534461 I Trifonov, J Uzunova [Successful full-term pregnancy in the Herlyn-Werner-Wunderlich syndrome: a case report and review of literature]. Akush Ginekol (Sofiia): 2014, 53 Suppl 2;42-5 PMID: 25510053 Gökhan Akkoyunlu, Filiz Tepekoy, Aydın Bebiş, Fatma Uysal Bilateral total ovarian hypoplasia in a Holstein Friesian heifer. Acta Histochem.: 2014; PMID: 25456311


Normal and abnormal epithelial differentiation in the female reproductive tract

Differentiation. 2011 Oct;82(3):117-26. doi: 10.1016/j.diff.2011.04.008. Epub 2011 May 25.

Kurita T. Source Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.


In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences. Copyright © 2011. Published by Elsevier B.V.

PMID 21612855

Vaginal microbiome of reproductive-age women

Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7. Epub 2010 Jun 3.

Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.


The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.

PMID 20534435

Background Reading

Search pubmed: Mullerian ducts


Revisiting old vaginal topics: conversion of the Müllerian vagina and origin of the "sinus" vagina

Cai Y. Int J Dev Biol. 2009;53(7):925-34. Review. PMID: 19598112 | IJDB


"Vaginal development has been a longstanding controversy, which hampers studies on vaginal diseases as well as cervical and uterine diseases. Most concerns center on: why is the vaginal epithelium different from the uterine epithelium; and where does the vagina originate from? It is commonly held that the rodent vagina has a dual origin: the cranial part is derived from the Mullerian duct (Mullerian vagina) and the caudal part derived from the urogenital sinus (sinus vagina). This concept was deduced from morphological observations. However, it cannot explain the difference between the Mullerian vagina and the uterus. Moreover, accumulating new data from genetic and molecular studies contradicts the urogenital sinus origin of the sinus vagina. The present review summarizes previous morphological observations and new findings from genetic and molecular studies, and addresses molecular mechanisms underlying the origin and organogenesis of the vagina in rodents. It provides evidence to show that the whole vagina is derived the Mullerian duct. BMP4 reshapes the intermediate mesoderm-derived Mullerian duct into the vaginal primordium. The latter thus exhibits different features from the uterus, including the stratified squamous epithelium and insensitivity to anti-Mullerian hormone. The sinus vagina is formed by extrinsic BMP4-mediated caudal extension of the Mullerian duct. The present review thus shows how a century of controversy over the origin and organogenesis of the vagina has been resolved. This new understanding will provide additional insight into genetic diseases and tumors of the female reproductive tract."

Fetal development of the female external urinary sphincter complex: an anatomical and histological study

Sebe P, Fritsch H, Oswald J, Schwentner C, Lunacek A, Bartsch G, Radmayr C. J Urol. 2005 May;173(5):1738-42; discussion 1742. PMID: 15821572


Experimental contributions to the study of the embryology of the vagina

Sánchez-Ferrer ML, Acién MI, Sánchez del Campo F, Mayol-Belda MJ, Acién P. Hum Reprod. 2006 Jun;21(6):1623-8. Epub 2006 Feb 13.

BACKGROUND: Acién's hypothesis, deduced from patients with malformations of the female genital tract, especially those with renal agenesis and ipsilateral blind hemivagina, affirms the embryology of the human vagina as deriving from the Wolffian ducts and the Müllerian tubercle and could explain the embryological origin of all the female genital malformations reported. In this study, we investigated the hypothesis in rats.

METHODS: Twenty-five pregnant rats were used to analyse female embryos (64) from day 15 (stage indifferent) to day 20 postcoitum (vagina completely formed). We performed transverse and longitudinal sections of embryos, haematoxylin-eosin tinction and immunohistochemical staining using markers specific to Wolffian derivatives. We also analysed the presence of these markers in the vagina of four adult rats.

RESULTS: The Müller ducts converge until they fuse into one tube, but caudally they diverge and finally they fuse with the 'urogenital sinus bulbs' that are actually the distal portion of the Wolffian ducts according to the immunohistochemical marking with GZ1 and GZ2. The Müllerian tubercle is observed between those elements. Then, the immunohistochemical staining can be seen all along the completely formed vagina, which is also observed in the vagina of the adult rat.

CONCLUSION: We prove the participation of Müller tubercle and Wolffian ducts in the formation of the vagina in rats, so we confirm experimentally Acién's hypothesis about the human vagina embryology.

PMID: 16476676

Lifetime changes in the vulva and vagina

Farage M, Maibach H. Arch Gynecol Obstet. 2006 Jan;273(4):195-202. Epub 2005 Oct 6. Review. PMID: 16208476

"The morphology and physiology of the vulva and vagina change over a lifetime. The most salient changes are linked to puberty, the menstrual cycle, pregnancy, and menopause. The cutaneous epithelia of the mons pubis, labia, and clitoris originate from the embryonic ectoderm and exhibit a keratinized, stratified structure similar to the skin at other sites. The mucosa of the vulvar vestibule, which originates from the embryonic endoderm, is non-keratinized. The vagina, derived from the embryonic mesoderm, is responsive to estrogen cycling. At birth, the vulva and vagina exhibit the effects of residual maternal estrogens. During puberty, the vulva and vagina acquire mature characteristics in a sequential fashion in response to adrenal and gonadal maturation. A trend to earlier pubertal onset has been observed in Western developed countries. In women of reproductive age, the vaginal mucosa responds to steroid hormone cycling, exhibiting maximal thickness and intracellular glycogen content at mid-cycle. Vulvar skin thickness remains unchanged but menstrual cycle-associated changes in ortho- and parakeratosis occur at the cytological level. The vulva and vagina further adapt to the needs of pregnancy and delivery. After menopause, tissue atrophy ensues. Post-menopausal changes in skin barrier function, skin hydration, and irritant susceptibility have been observed on exposed skin but not on the vulva. Nevertheless, older women with incontinence are at increased risk for developing incontinence dermatitis. A combination of factors, such as tissue atrophy, slower dissipation of excess skin hydration, shear forces associated with limited mobility, and lower tissue regeneration capacity increase the risk of morbidity from incontinence dermatitis in older women."

Baseline dimensions of the human vagina

Barnhart KT, Izquierdo A, Pretorius ES, Shera DM, Shabbout M, Shaunik A. Hum Reprod. 2006 Jun;21(6):1618-22. Epub 2006 Feb 14. PMID: 16478763

magnetic resonance imaging (MRI) to quantify distribution of a vaginal gel. Seventy-seven MRI scans were performed on 28 women before gel application to establish baseline vaginal measurements. Average dimensions were calculated for each woman and for the population. The influence of potential covariates (age, height, weight and parity) on these dimensions was assessed. ...Mean vaginal length from cervix to introitus was 62.7 mm. Vaginal width was largest in the proximal vagina (32.5 mm), decreased as it passed through the pelvic diaphragm (27.8 mm) and smallest at the introitus (26.2 mm)."


New concepts on the development of the vagina

Shapiro E, Huang H, Wu XR. Adv Exp Med Biol. 2004;545:173-85. Review. No abstract available. PMID: 15086027

Fetal development of the female external urinary sphincter complex: an anatomical and histological study

Sebe P, Fritsch H, Oswald J, Schwentner C, Lunacek A, Bartsch G, Radmayr C. J Urol. 2005 May;173(5):1738-42; discussion 1742. PMID: 15821572

  • Helper function of the Wolffian ducts and role of androgens in the development of the vagina. Drews U. Sex Dev. 2007;1(2):100-10. PMID: 18391520
"Here experiments with the complete androgen receptor defect in the testicular feminisation (Tfm) mouse are reported which show that the vagina is formed by caudal migration of Wolffian and Müllerian ducts. The cranial ends of the Wolffian ducts successively regress while the Müllerian ducts fuse to form the vagina. Immunohistochemistry of the androgen receptor reveals that the caudal ends of the Wolffian ducts remain in the indifferent stage and therefore have been mistaken as sinuvaginal bulbs. The Wolffian ducts do not contribute to the vagina itself but have a helper function during downward movement of the vaginal bud in the female. In the male the caudal ends serve as androgen operated switch for the negative control of vaginal development. The results indicate that the rudimentary vagina in the complete androgen insensitivity syndrome (CAIS) corresponds to non obliterated caudal ends of the Müllerian ducts. Selective atresia of the vagina in the MRKH (Mayer-Rokitansky-Kuster-Hauser) syndrome may be explained by the failure of Wolffian and Müllerian ducts to descend caudally"


Preliminary Note on the Development of the Clitoris, Vagina, and Hymen

J Anat Physiol. 1896 Oct;31(Pt 1):18-28.11.

Hart DB.

PMID: 17232227

PMCID: PMC1327808

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome

text and table below from

Surgical creation of a neovagina A number of techniques are appropriate for the correction of vaginal agenesis and there is no consensus regarding the best option, the approach being most often based on the surgeon's experience. Three methods are currently in use:

- The Abbe-McIndoe operation: this involves the dissection of a space between the rectum and the bladder, placement of a mold covered with a skin graft into the space, and diligent postoperative vaginal dilatation. Modifications of this procedure rely on spontaneous epithelialization or on the use of different materials such as peritoneum [111], minora labia grafting, or synthetic materials [112,113].

- The Vecchietti operation is a mixture of surgical and nonsurgical methods. It has been performed frequently in Europe over the last 20 years [70]. This procedure involves the creation of a neovagina via dilatation with a traction device attached to the abdomen, sutures placed subperitoneally by laparotomy, and a plastic olive placed in the vaginal dimple. A laparoscopic or celioscopic modification is often preferred and leads to comparable results [114].

- Sigmoidal colpoplasty: this technique involves vaginal replacement or creation of a neovagina by grafting a 12–18 cm long segment of sigmoid [115], providing that a single and/or left pelvic kidney does not impair the procedure. Sigmoidal colpoplasty is believed to be an efficient procedure giving excellent results, although complete adequacy for coital function often requires prolonged care and support [116].

Summary of differential diagnosis between MRKH syndrome and isolated vaginal atresia, WNT4 syndrome, and androgen insensitivity syndrome.
Isolated vaginal atresia
WNT4 syndrome
Androgen insensitivity
Upper vagina
Masculinized ovary
Breast development
Pubic-hair development
46, XX
46, XX
46, XX
46, XY
Morcel et al. Orphanet Journal of Rare Diseases 2007 2:13   doi:10.1186/1750-1172-2-13

Complex malformations of the female genital tract. New types and revision of classification. Acién P, Acién M, Sánchez-Ferrer M. Hum Reprod. 2004 Oct;19(10):2377-84. Epub 2004 Aug 27. PMID: 15333604


The development of the human vagina

BULMER D. J Anat. 1957 Oct;91(4):490-509. No abstract available. PMID: 13475148 | PMCID: 1244904
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