Parr B A, McMahon A P
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature. 1998 Oct 15;395(6703):707-10. doi: 10.1038/27221.
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. The receptor for Müllerian-inhibiting substance is expressed by mesenchymal cells underlying the Müllerian duct that are thought to mediate regression of the duct. Mutations that inactivate either Müllerian-inhibiting substance or its receptor allow development of the female reproductive tract in males. These pseudohermaphrodites are frequently infertile because sperm passage is blocked by the presence of the female reproductive system. 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.
哺乳动物发育的一个重要特征是由苗勒氏管和中肾管发育出两性异形的生殖道。在雌性中，苗勒氏管发育为输卵管、子宫、子宫颈和阴道上段，而中肾管退化。在雄性中，睾酮促进中肾管分化为附睾、输精管和精囊。睾丸的支持细胞产生苗勒氏管抑制物质，刺激雄性苗勒氏管退化。苗勒氏管抑制物质的受体由苗勒氏管下方的间充质细胞表达，这些细胞被认为介导了苗勒氏管的退化。使苗勒氏管抑制物质或其受体失活的突变会导致雄性发育出雌性生殖道。这些假两性畸形个体通常不育，因为精子通道被雌性生殖系统的存在所阻断。我们在此表明，缺乏信号分子Wnt-7a的雄性小鼠由于缺乏苗勒氏管抑制物质的受体而无法使苗勒氏管退化。Wnt7a基因缺陷的雌性小鼠不育，原因是输卵管和子宫发育异常，而这两者都是苗勒氏管的衍生物。因此，我们提出Wnt-7a信号传导使苗勒氏管实现两性异形发育。
