Molecular genetics of Müllerian duct formation regression and differentiation

摘要

The Müllerian duct forms the female reproductive tract consisting of the oviducts, uterus, cervix and upper vagina. Female reproductive tract function is vital to fertility, providing the site of fertilization, embryo implantation and fetal development. Developmental defects in the formation, and diseases of the female reproductive tract, including cancer and endometriosis, are prevalent in humans and can result in infertility and death. Further, because the Müllerian ducts are initially formed regardless of genotypic sex, mesenchymal-to-epithelial signaling is required in males to mediate Müllerian duct regression and prevents the development of Müllerian-derived organs. In males, defects in Müllerian duct regression result in the retention of female reproductive tract organs and have been described in several human syndromes. Although to date not reported in humans, ectopic activation of Müllerian duct regression signaling components in females can result in aplasia of the female reproduction tract. Clearly, Müllerian duct development is important to human health, however the molecular mechanisms remain largely undetermined. Molecular genetics studies of human disease and mouse models have provided new insights into molecular signaling during Müllerian duct development, regression and differentiation. This review will provide an overview of Müllerian duct development and important genes and signaling mechanisms involved.