 | ENVIRONMENTAL HORMONES: THE SCIENTIFIC BASIS OF ENDOCRINE DISRUPTION
Copyright © 2001 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 948:13-31 (2001)
© 2001 New York Academy of Sciences
External Genitalia Formation
Role of Fibroblast Growth Factor, Retinoic Acid Signaling, and Distal Urethral Epithelium
YUKIKO OGINOa,
KENTARO SUZUKIa,
RYUMA HARAGUCHIa,
YOSHIHIKO SATOHa,
PASCAL DOLLEb AND
GEN YAMADAa
aCenter for Animal Resources and Development (CARD), Kumamoto University, Kumamoto 860-0811, Japan
bInstitut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP/College de France, BP163 67404 ILLKIRCH, Cedex, France
Address for correspondence: Dr. Gen Yamada, Center for Animal Resources and Development (CARD), Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan. Voice: 81-96-373 6556; fax: 81-96-373 6560.
gen{at}kaiju.medic.kumamoto-u.ac.jp
The process of fetal external genitalia development might be divided into two processes. The first process accomplishes the initial outgrowth of the anlage, genital tubercle (GT). Previous analysis suggests that the distal urethral epithelium (DUE) of the GT, the Fgf8-expressing region, regulates the outgrowth of the GT. The second process eventually generates the sexually dimorphic development of the external genitalia, which is dependent on the action of steroid hormones. Several key genes, for example, RARs, RXRs, RALDH2, and CYP26, were dynamically expressed during GT development. The teratogenic dose of RA at 9.0 d.p.c. induced a drastic malformation of the urethral plate during GT formation, but did not show gross abnormalities in its outgrowth. In RA-treated embryos, Fgf8 expression was still detected in the distal GT regions. Possible regulatory roles of the FGF and RA signaling systems in external genitalia formation are discussed.
Key Words: external genitalia • genital tubercle • penis • urethral plate • Fgf • retinoic acid • androgen • hypospadias
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