Maya Overland1, Yi Li1, Mei Cao1, Joel Shen1, Xuan Yue1, Sisir Botta1, Adriane Sinclair1, Gerald Cunha1, Laurence Baskin2. 1. Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California. 2. Division of Pediatric Urology, University of California-San Francisco Benioff Children's Hospital, San Francisco, California. Electronic address: lbaskin@urology.ucsf.edu.
Abstract
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.
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.
Authors: Gerald R Cunha; Gail Risbridger; Hong Wang; Ned J Place; Mel Grumbach; Tristan J Cunha; Mary Weldele; Al J Conley; Dale Barcellos; Sanjana Agarwal; Argun Bhargava; Christine Drea; Geoffrey L Hammond; Penti Siiteri; Elizabeth M Coscia; Michael J McPhaul; Laurence S Baskin; Stephen E Glickman Journal: Differentiation Date: 2014-02-28 Impact factor: 3.880
Authors: James Sharpe; Ulf Ahlgren; Paul Perry; Bill Hill; Allyson Ross; Jacob Hecksher-Sørensen; Richard Baldock; Duncan Davidson Journal: Science Date: 2002-04-19 Impact factor: 47.728
Authors: Laurence Baskin; Joel Shen; Adriane Sinclair; Mei Cao; Xin Liu; Ge Liu; Dylan Isaacson; Maya Overland; Yi Li; Gerald R Cunha Journal: Differentiation Date: 2018-08-23 Impact factor: 3.880
Authors: Gerald R Cunha; Adriane Sinclair; Will A Ricke; Stanley J Robboy; Mei Cao; Laurence S Baskin Journal: Differentiation Date: 2019-09-06 Impact factor: 3.880