ArticleProceedings of the National Academy of Sciences of the United States of America2016
Spatiotemporal dynamics of androgen signaling underlie sexual differentiation and congenital malformations of the urethra and vagina.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Epithelial and mesenchymal compartments of the developing bladder and urethra display spatially distinct gene expression patterns.Developmental biology · 2025Article
- Androgen receptor ubiquitination links KCTD13 to genitourinary tract defects.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Management of High Urogenital Sinus in Adults: A Scoping Review.Medicina (Kaunas, Lithuania) · 2025Article
- Urogenital sinus malformation: From development to management.Intractable & rare diseases research · 2023Review
- Androgen-regulatediScience · 2022Article
- One Tool for Many Jobs: Divergent and Conserved Actions of Androgen Signaling in Male Internal Reproductive Tract and External Genitalia.Frontiers in endocrinology · 2022Review
- Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Persistent Labial Minora Fusion in Reproductive Age Women: A Retrospective Case Series of Nine Patients and Review of Literature.Organogenesis · 2021Review
- Meeting report on the NIDDK/AUA Workshop on Congenital Anomalies of External Genitalia: challenges and opportunities for translational research.Journal of pediatric urology · 2020Review
- Prenatal low-dose methyltestosterone, but not dihydrotestosterone, treatment induces penile formation in female mice and guinea pigs†.Biology of reproduction · 2020Article
- Reproductive tract biology: Of mice and men.Differentiation; research in biological diversityReview
- Molecular mechanisms of development of the human fetal female reproductive tract.Differentiation; research in biological diversityArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Disorders of sex development (DSDs) are congenital anomalies that affect sexual differentiation of genitourinary organs and secondary sex characters. A common cause of female genital virilization is congenital adrenal hyperplasia (CAH), in which excess androgen production during development of 46XX females can result in vaginal atresia, masculinization of the urethra, a single urogenital sinus, and clitoral hypertrophy or ambiguous external genitalia. Development of the vagina depends on sexual differentiation of the urogenital sinus ridge, an epithelial thickening that forms where the sex ducts attach to the anterior urethra. In females, the sinus ridge descends posteriorly to allow the vaginal opening to form in the vulva, whereas in males and in females with CAH, androgens inhibit descent of the sinus ridge. The mechanisms that regulate development of the female urethra and vagina are largely unknown. Here we show that the timing and duration of, and the cell population targeted by, androgen signaling determine the position of vaginal attachment to the urethra. Manipulations of androgen signaling in utero reveal a temporal window of development when sinus ridge fate is determined. Cell type-specific genetic deletions of androgen receptor (Ar) identify a subpopulation of mesenchymal cells that regulate sinus ridge morphogenesis. These results reveal a common mechanism that coordinates development of the vagina and feminization of the urethra, which may account for development of a single urogenital sinus in females exposed to excessive androgen during a critical period of prenatal development.
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