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Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation\u2010PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m\n                      <jats:sup>6<\/jats:sup>\n                      A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m\n                      <jats:sup>6<\/jats:sup>\n                      A demethylase ALKBH5 and decreased expression of the m\n                      <jats:sup>6<\/jats:sup>\n                      A reader protein YTHDF2. YTHDF2 directly bind to the m\n                      <jats:sup>6<\/jats:sup>\n                      A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective\n                      <jats:italic>Ezh2<\/jats:italic>\n                      depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up\u2010regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m\n                      <jats:sup>6<\/jats:sup>\n                      A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2\/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m\n                      <jats:sup>6<\/jats:sup>\n                      A modification of EZH2 mRNA.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1564","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T05:19:44Z","timestamp":1707715184000},"source":"Crossref","is-referenced-by-count":30,"title":["The involvement of RNA N6\u2010methyladenosine and histone methylation modification in decidualization and endometriosis\u2010associated infertility"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-6948","authenticated-orcid":false,"given":"Xiang","family":"Lin","sequence":"first","affiliation":[{"name":"Assisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run 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