Oviductal estrogen receptor ? signaling prevents protease-mediated embryo death.

ABSTRACT: Development of uterine endometrial receptivity for implantation is orchestrated by cyclic steroid hormone-mediated signals. It is unknown if these signals are necessary for oviduct function in supporting fertilization and preimplantation development. Here we show that conditional knockout (cKO) mice lacking estrogen receptor ? (ER?) in oviduct and uterine epithelial cells have impaired fertilization due to a dramatic reduction in sperm migration. In addition, all successfully fertilized eggs die before the 2-cell stage due to persistence of secreted innate immune mediators including proteases. Elevated protease activity in cKO oviducts causes premature degradation of the zona pellucida and embryo lysis, and wild-type embryos transferred into cKO oviducts fail to develop normally unless rescued by concomitant transfer of protease inhibitors. Thus, suppression of oviductal protease activity mediated by estrogen-epithelial ER? signaling is required for fertilization and preimplantation embryo development. These findings have implications for human infertility and post-coital contraception.

SUBMITTER: Winuthayanon W 

PROVIDER: S-EPMC4718728 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature