Canalization of the vestibular plate in the absence of urethral fusion characterizes development of the human clitoris: the single zipper hypothesis
Open accessAbstract
PURPOSE: We characterized the early gestation development of the female external genitalia using optical projection tomography to visualize anatomical structures at high resolution. MATERIALS AND METHODS: First and early second trimester human female fetal external genitalia were collected with consent after voluntary termination. Specimens labeled with anti-E-Cadherin antibody underwent analysis with optical projection tomography. Histological sections were immunostained for androgen receptor, 5α-reductase, Ki67 for proliferation and Caspase 3 for apoptosis. RESULTS: Three-dimensional reconstructions demonstrated proximal to distal canalization of the epithelial vestibular plate and formation of a vestibular groove, which remained open. Ki67 was observed throughout with greatest density in the dorsal vestibular plate at the level of the opening groove. Staining for Caspase 3 was minimal in all sections. Androgen receptor staining was seen throughout the mesenchyme and in the apical epithelium of the dorsal vestibular groove. Throughout the epithelium and epidermis 5α-reductase staining was observed. CONCLUSIONS: Early development of the external genitalia in the female is analogous to that in the male, demonstrating a similar opening zipper driving canalization of the vestibular plate with localized epithelial proliferation in the absence of significant apoptosis. Thus we hypothesize that the mechanism underlying the opening zipper must be androgen independent and the absence of androgen driven urethral fusion characterizes the normal development of the human clitoris.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, male-specific morphological differentiation of the genital tubercle/penis begins around 10 weeks of gestation, with closure of the urethral groove, and is complete by about gestation weeks 15-16.5.
“In humans, male-specific morphological differentiation of the genital tubercle/penis begins around 10 weeks of gestation (i.e., 8 weeks postconception), with closure of the urethral groove [6,7]. The process is complete by about gestation weeks 15–16.5 [6,7]”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies
Sharpe, J. A., Ahlgren, U., Perry, P., Hill, B., Ross, A., Hecksher‐Sørensen, J., Baldock, R., & Davidson, D. R. (2002) · Science · doi:10.1126/science.1068206 · Cited by 1,158 · see citing works
ANATOMICAL STUDIES OF THE HUMAN CLITORIS
Baskin, L. S., Erol, A., LI, Y. W., LIU, W. H., Kurzrock, E. A., & Cunha, G. R. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)68052-2 · Cited by 240 · see citing works
Self-citationUrethral seam formation and hypospadias
Baskin, L. S., Erol, A., Jegatheesan, P., Li, Y., Liu, W., & Cunha, G. R. (2001) · Cell and Tissue Research · doi:10.1007/s004410000345 · Cited by 136 · see citing works
Self-citationSeifert, A. W., Bouldin, C. M., Choi, K., Harfe, B. D., & Cohn, M. J. (2009) · Development · doi:10.1242/dev.042291 · Cited by 107 · see citing works
Li, Y., Sinclair, A., Cao, M., Shen, J., Choudhry, S., Botta, S., Cunha, G., & Baskin, L. (2015) · Journal of Urology · doi:10.1016/j.juro.2014.09.108 · Cited by 97 · see citing works
Self-citationImproving the Accuracy of Fetal Foot Length to Confirm Gestational Duration
Drey, E. A., Kang, M.-S., McFarland, W., & Darney, P. D. (2005) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000154159.75022.11 · Cited by 75 · see citing works
The Effect of Testosterone on Androgen Receptors and Human Penile Growth
Baskin, L. S., Sutherland, R. S., DiSandro, M., Hayward, S. W., Lipschutz, J. H., & Cunha, G. R. (1997) · The Journal of Urology · doi:10.1097/00005392-199709000-00108 · Cited by 71 · see citing works
Self-citationThe Effect of Testosterone on Androgen Receptors and Human Penile Growth
Baskin, L. S., Sutherland, R. S., DiSandro, M., Hayward, S. W., Lipschutz, J. H., & Cunha, G. R. (1997) · The Journal of Urology · doi:10.1016/s0022-5347(01)64400-8 · Cited by 70 · see citing works
Self-citationSexually dimorphic expression of Mafb regulates masculinization of the embryonic urethral formation
Suzuki, K., Numata, T., Suzuki, H., Raga, D. D., Ipulan, L. A., Yokoyama, C., Matsushita, S., Hamada, M., Nakagata, N., Nishinakamura, R., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413273111 · Cited by 59 · see citing works
Development of the Human Anterior Urethra
Altemus, A. R., & Hutchins, G. M. (1991) · The Journal of Urology · doi:10.1016/s0022-5347(17)38008-4 · Cited by 54 · see citing works
ANATOMICAL STUDIES OF THE HUMAN CLITORIS
Baskin, L. S., Erol, A., LI, Y. W., et al. (1999) · The Journal of Urology · doi:10.1097/00005392-199909000-00014 · Cited by 51 · see citing works
Self-citationDevelopment of the external genitalia: Perspectives from the spotted hyena (Crocuta crocuta)
Cunha, G. R., Risbridger, G. P., Wang, H., Place, N. J., Grumbach, M. M., Cunha, T. J., Weldele, M. L., Conley, A. J., Barcellos, D., Agarwal, S., et al. (2014) · Differentiation · doi:10.1016/j.diff.2013.12.003 · Cited by 43 · see citing works
Self-citationMicrosatellites proximal to leptin and leptin receptor as risk factors for spina bifida
Shaw, G. M., Barber, R. C., Todoroff, K., Lammer, E. J., & Finnell, R. H. (2000) · Teratology · doi:10.1002/(sici)1096-9926(200003)61:3 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [6]Ridley CM Neill SM Lewis FM Ridley’s The Vulva 2009 3rd Hoboken Wiley-Blackwell
- [12]Conte FA Grumbach MM Gardner DG Disorders of sexual determination and differentiation Greenspan’s Basic and Clinical Endocrinology 2007 8th New York McGraw-Hill 562 610
Cited by
Sorted by citations
Alternative (backdoor) androgen production and masculinization in the human fetus
O’Shaughnessy, P. J., Antignac, J. P., Le Bizec, B., Morvan, M.-L., Svechnikov, K., Söder, O., Savchuk, I., Monteiro, A., Soffientini, U., Johnston, Z. C., et al. (2019) · PLOS Biology · doi:10.1371/journal.pbio.3000002 · Cited by 177 · see citing works
- Authors
- Overland, M., Li, Y., Cao, M., Shen, J., Yue, X., Botta, S., Sinclair, A., Cunha, G., & Baskin, L.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Baskin, Laurence
- Venue
- Journal of Urology
- Published
- 2016-04
- Volume
- 195
- Issue
- 4 Part 2
- Pages
- 1275-1283
- ISSN
- 0022-5347 (ISSN-L)
- 1527-3792
- PMC
- PMC5087991
- OpenAlex
- W2279927698
- Cited by
- 38
- References
- 13
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 4 · 2019: 9 · 2018: 6 · 2017: 4 · 2016: 1
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Urology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007618)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-058105, R01DK058105)
- Topics
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Surgery › Congenital Anomalies and Fetal Surgery
- Keywords
- female external genitalia, androgen receptor, 5α-reductase, epithelial cell proliferation, apoptosis
- MeSH terms
- Clitoris, Female, Gestational Age, Humans, Urethra, Imaging, Three-Dimensional, Tomography, Optical
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
