Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a

Abstract

An important feature of mammalian development is the generation of sexually dimorphic reproductive tracts from the Müllerian and Wolffian ducts. In females, Müllerian ducts develop into the oviduct, uterus, cervix and upper vagina, whereas Wolffian ducts regress. In males, testosterone promotes differentiation of Wolffian ducts into the epididymis, vas deferens and seminal vesicle. The Sertoli cells of the testes produce Müllerian-inhibiting substance, which stimulates Müllerian duct regression in males^1,2,3,4. The receptor for Müllerian-inhibiting substance is expressed by mesenchymal cells underlying the Müllerian duct that are thought to mediate regression of the duct^5,6,7. Mutations that inactivate either Müllerian-inhibiting substance or its receptor allow development of the female reproductive tract in males^8,9,10,11,12. These pseudohermaphrodites are frequently infertile because sperm passage is blocked by the presence of the female reproductive system⁹,¹⁰,¹². Here we show that male mice lacking the signalling molecule Wnt-7a fail to undergo regression of the Müllerian duct as a result of the absence of the receptor for Müllerian-inhibiting substance. Wnt7a-deficient females are infertile because of abnormal development of the oviduct and uterus, both of which are Müllerian duct derivatives. Therefore, we propose that signalling by Wnt-7a allows sexually dimorphic development of the Müllerian ducts.