Journal article
Oviductal estrogen receptor α signaling prevents protease-mediated embryo death
eLife, Vol.4(2015), pp.e10453-e10453
12/01/2015
Handle:
https://hdl.handle.net/2376/106099
PMCID: PMC4718728
PMID: 26623518
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 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.
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Details
- Title
- Oviductal estrogen receptor α signaling prevents protease-mediated embryo death
- Creators
- Wipawee Winuthayanon - School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, United StatesMiranda L Bernhardt - Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesElizabeth Padilla-Banks - Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesPage H Myers - Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesMatthew L Edin - Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesFred B Lih - Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, USASylvia C Hewitt - Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesKenneth S Korach - Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesCarmen J Williams - Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States
- Publication Details
- eLife, Vol.4(2015), pp.e10453-e10453
- Academic Unit
- Center for Reproductive Biology; Molecular Biosciences, School of
- Publisher
- England
- Grant note
- ZIA ES102405 / Intramural NIH HHS 1ZIAES102405 / PHS HHS 1ZIAES050167 / PHS HHS 1ZIAES025034 / PHS HHS 1ZIAES70065 / PHS HHS ZIA ES050167 / Intramural NIH HHS ZIA ES070065 / Intramural NIH HHS ZIA ES025034 / Intramural NIH HHS
- Identifiers
- 99900546890101842
- Language
- English
- Resource Type
- Journal article