title: Canalization of the Vestibular Plate in the Absence of Urethral Fusion Characterizes Development of the Human Clitoris: The Single Zipper Hypothesis.
abstract: OBJECTIVE
  We characterized the early gestation development of the female external genitalia using optical projection tomography to visualize anatomical structures at high resolution.
  
  
  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.
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Maya
authors.initials: M
authors.lastname: Overland
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Mei
authors.initials: M
authors.lastname: Cao
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Joel
authors.initials: J
authors.lastname: Shen
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yue
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Sisir
authors.initials: S
authors.lastname: Botta
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Adriane
authors.initials: A
authors.lastname: Sinclair
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California.
authors.forename: Gerald
authors.initials: G
authors.lastname: Cunha
authors.affiliation: Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California. Electronic address: lbaskin@urology.ucsf.edu.
authors.forename: Laurence
authors.initials: L
authors.lastname: Baskin
mesh_terms: D002987:Clitoris / Q000196:embryology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D021621:Imaging, Three-Dimensional; D041622:Tomography, Optical; D014521:Urethra / Q000196:embryology
keywords: androgens; clitoris; embryonic and fetal development; female; genitalia; tomography, optical