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Despite our improved understanding of the genetic regulation of implantation downstream of the action of hormones, we do not know much about the epigenetic regulation that occurs during early pregnancy. To investigate the role of the N6\u2010methyladenosine (m6A) RNA modification in embryo implantation, we generated mice with conditional deletion of\n                    <jats:italic>Mettl14<\/jats:italic>\n                    , a core component of the m6A writer complex, in the uterus. These mice were infertile due to implantation failure. We showed that\n                    <jats:italic>Mettl14<\/jats:italic>\n                    \u2010deficient uteri had aberrant upregulation of estrogen receptor \u03b1 (ER\u03b1) signaling and ER\u03b1 phosphorylation, but progesterone receptor (PGR) signaling was largely unaffected. Additionally,\n                    <jats:italic>Mettl14<\/jats:italic>\n                    deletion led to abnormal activation of the innate immune pathway in\n                    <jats:italic>Mettl14<\/jats:italic>\n                    \u2010deficient uteri. This effect was accompanied by the infiltration of immune cells, such as macrophages and dendritic cells, into the basal region of the endometrial epithelium. Methylated RNA immunoprecipitation sequencing (MeRIP\u2010seq) showed that genes involved in the innate immune response had decreased m6A peaks in\n                    <jats:italic>Mettl14<\/jats:italic>\n                    \u2010deficient mice. These results suggest that\n                    <jats:italic>Mettl14<\/jats:italic>\n                    plays a crucial role in successful implantation by precisely regulating both ER\u03b1 signaling and innate immunity in the uterus.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300735r","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T11:38:14Z","timestamp":1689248294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Aberrant activation of estrogen receptor\u2010\u03b1 signaling in Mettl14\u2010deficient uteri impairs embryo implantation"],"prefix":"10.1096","volume":"37","author":[{"given":"Ryosuke","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation Gunma University  Maebashi 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