biostudies-literatureWinuthayanon WNational Institute of Environmental Health SciencesIntramural NIH HHSPHS HHSe10453https://www.ebi.ac.uk/biostudies/studies/S-EPMC4718728biostudies-literatureUnknown4Development 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 reseLifeOviductal estrogen receptor α signaling prevents protease-mediated embryo death.PMC47187281ZIAES70065ZIA ES070065ZIA ES050167ZIA ES1024051ZIAES0250341ZIAES102405ZIA ES0250341ZIAES050167Winuthayanon WHewitt SCLih FBEdin MLWilliams CJPadilla-Banks EBernhardt MLKorach KSMyers PHfalseOviductal estrogen receptor α signaling prevents protease-mediated embryo death.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 res2015-01-01T00:00:00Z2015 Dec2026-06-14T03:17:55.188Z2026-06-14T03:09:03.123ZS-EPMC47187282662351810.7554/eLife.10453