Oviductal 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/10453 |
| _version_ | 1811228060300607488 |
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| author | Wipawee Winuthayanon Miranda L Bernhardt Elizabeth Padilla-Banks Page H Myers Matthew L Edin Fred B Lih Sylvia C Hewitt Kenneth S Korach Carmen J Williams |
| author_facet | Wipawee Winuthayanon Miranda L Bernhardt Elizabeth Padilla-Banks Page H Myers Matthew L Edin Fred B Lih Sylvia C Hewitt Kenneth S Korach Carmen J Williams |
| author_sort | Wipawee Winuthayanon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:52:09Z |
| format | Article |
| id | doaj.art-7b93fb6fdb574e07b6fc3a3f87f88db2 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:52:09Z |
| publishDate | 2015-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7b93fb6fdb574e07b6fc3a3f87f88db22022-12-22T03:37:48ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.10453Oviductal estrogen receptor α signaling prevents protease-mediated embryo deathWipawee Winuthayanon0https://orcid.org/0000-0002-5196-8471Miranda L Bernhardt1https://orcid.org/0000-0001-5424-5685Elizabeth Padilla-Banks2Page H Myers3Matthew L Edin4Fred B Lih5Sylvia C Hewitt6https://orcid.org/0000-0001-7713-0805Kenneth S Korach7Carmen J Williams8https://orcid.org/0000-0001-6440-7086Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States; School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, United StatesReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesComparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesImmunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United StatesDevelopment 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.https://elifesciences.org/articles/10453oviductestrogen receptorpreimplantation embryofertilizationinnate immunity |
| spellingShingle | Wipawee Winuthayanon Miranda L Bernhardt Elizabeth Padilla-Banks Page H Myers Matthew L Edin Fred B Lih Sylvia C Hewitt Kenneth S Korach Carmen J Williams Oviductal estrogen receptor α signaling prevents protease-mediated embryo death eLife oviduct estrogen receptor preimplantation embryo fertilization innate immunity |
| title | Oviductal estrogen receptor α signaling prevents protease-mediated embryo death |
| title_full | Oviductal estrogen receptor α signaling prevents protease-mediated embryo death |
| title_fullStr | Oviductal estrogen receptor α signaling prevents protease-mediated embryo death |
| title_full_unstemmed | Oviductal estrogen receptor α signaling prevents protease-mediated embryo death |
| title_short | Oviductal estrogen receptor α signaling prevents protease-mediated embryo death |
| title_sort | oviductal estrogen receptor α signaling prevents protease mediated embryo death |
| topic | oviduct estrogen receptor preimplantation embryo fertilization innate immunity |
| url | https://elifesciences.org/articles/10453 |
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