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

Wipawee WinuthayanonMiranda L BernhardtElizabeth Padilla-BanksPage H MyersMatthew L EdinFred B LihSylvia C HewittKenneth S KorachCarmen J Williams
Published in: eLife (2015)
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.
Keyphrases
  • estrogen receptor
  • wild type
  • innate immune
  • single cell
  • type diabetes
  • stem cells
  • adipose tissue
  • bone marrow
  • pregnant women
  • mesenchymal stem cells
  • skeletal muscle
  • induced pluripotent stem cells
  • high fat diet induced