{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:13:51Z","timestamp":1778120031662,"version":"3.51.4"},"reference-count":60,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T00:00:00Z","timestamp":1703289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070844"],"award-info":[{"award-number":["32070844"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R & D Program of China","doi-asserted-by":"crossref","award":["2020YFA0803900"],"award-info":[{"award-number":["2020YFA0803900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Innovative Research Team","award":["SHSMU-ZLCX20210201"],"award-info":[{"award-number":["SHSMU-ZLCX20210201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Progesterone synthesized in the placenta is essential for pregnancy maintenance. CYP11A1 is a key enzyme in progesterone synthesis, and its expression increases greatly during trophoblast syncytialization. However, the underlying mechanism remains elusive. Here, we demonstrated that passive demethylation of CYP11A1 promoter accounted for the upregulation of CYP11A1 expression during syncytialization with the participation of the transcription factor C\/EBP\u03b1. We found that the methylation rate of a CpG locus in the CYP11A1 promoter was significantly reduced along with decreased DNA methyltransferase 1 (DNMT1) expression and its enrichment at the CYP11A1 promoter during syncytialization. DNMT1 overexpression not only increased the methylation of this CpG locus in the CYP11A1 promoter, but also decreased CYP11A1 expression and progesterone production. In silico analysis disclosed multiple C\/EBP\u03b1 binding sites in both CYP11A1 and DNMT1 promoters. C\/EBP\u03b1 expression and its enrichments at both the DNMT1 and CYP11A1 promoters were significantly increased during syncytialization. Knocking-down C\/EBP\u03b1 expression increased DNMT1 while it decreased CYP11A1 expression during syncytialization. Conclusively, C\/EBP\u03b1 plays a dual role in the regulation of CYP11A1 during syncytialization. C\/EBP\u03b1 not only drives CYP11A1 expression directly, but also indirectly through downregulation of DNMT1, which leads to decreased methylation in the CpG locus of the CYP11A1 promoter, resulting in increased progesterone production during syncytialization.<\/jats:p>","DOI":"10.1210\/endocr\/bqad195","type":"journal-article","created":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T08:36:46Z","timestamp":1703493406000},"source":"Crossref","is-referenced-by-count":8,"title":["The Role of DNMT1 and C\/EBP\u03b1 in the Regulation of <i>CYP11A1<\/i> Expression During Syncytialization of Human Placental Trophoblasts"],"prefix":"10.1210","volume":"165","author":[{"given":"Ya-Nan","family":"Zhu","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200135 , P.R. China"},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai 200135 , P.R. China"},{"name":"Center for Reproductive Medicine, Xiangyang Central Hospital, Hubei University of Arts and Science , Xiangyang, Hubei 441021 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Pan","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200135 , P.R. China"},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai 200135 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Wen","family":"Gan","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200135 , P.R. China"},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai 200135 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200135 , P.R. China"},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai 200135 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-9237","authenticated-orcid":false,"given":"Wang-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200135 , P.R. China"},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai 200135 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2727-141X","authenticated-orcid":false,"given":"Kang","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200135 , P.R. China"},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai 200135 , P.R. 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