TY - JOUR TI - Oviductal estrogen receptor α signaling prevents protease-mediated embryo death AU - Winuthayanon, Wipawee AU - Bernhardt, Miranda L AU - Padilla-Banks, Elizabeth AU - Myers, Page H AU - Edin, Matthew L AU - Lih, Fred B AU - Hewitt, Sylvia C AU - Korach, Kenneth S AU - Williams, Carmen J A2 - Rossant, Janet VL - 4 PY - 2015 DA - 2015/12/01 SP - e10453 C1 - eLife 2015;4:e10453 DO - 10.7554/eLife.10453 UR - https://doi.org/10.7554/eLife.10453 AB - 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 α (ERα) 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 ERα signaling is required for fertilization and preimplantation embryo development. These findings have implications for human infertility and post-coital contraception. KW - oviduct KW - estrogen receptor KW - preimplantation embryo KW - fertilization KW - innate immunity JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -