{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:23:58Z","timestamp":1787822638055,"version":"build-2784847793"},"reference-count":57,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,8,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Preeclampsia (PE) is a serious pregnancy\u2010specific hypertensive disorder with unclear pathogenesis. Mitochondrial dysfunction in trophoblasts is implicated in PE. This study aimed to explore the functional mechanism of succinate dehydrogenase complex subunit D (SDHD) in PE. Placental tissues were obtained from PE patients and normotensive pregnant controls. Hypoxia\/reoxygenation (H\/R) injury was induced in HTR\u20108\/Svneo cells, and a preeclampsia\u2010like rat model was established using reduced uterine perfusion pressure (RUPP) surgery. Cell viability, proliferation, migration, and invasion were evaluated using CCK\u20108, EdU staining, wound healing, and Transwell assays. Mitochondrial function was assessed by measuring reactive oxygen species (ROS) production, membrane potential, oxygen consumption rate (OCR), mitochondrial DNA (mtDNA) copy number, and electron transport chain (ETC) complex activities. Interactions were examined by co\u2010immunoprecipitation (Co\u2010IP) and chromatin immunoprecipitation (ChIP), while SDHD promoter methylation was assessed using methylation\u2010specific PCR (MSP). SDHD expression was downregulated in human PE placentas and in H\/R\u2010induced HTR\u20108\/Svneo cells. SDHD overexpression ameliorated H\/R\u2010induced mitochondrial dysfunction, restored HTR\u20108\/Svneo cell proliferation, migration, and invasion, and alleviated disease features in RUPP rats. Mechanistically, MBD1 recruited DNMT1 to the SDHD promoter, leading to transcriptional repression of SDHD. The impairment of mitochondrial function and trophoblast behaviors of MBD1 knockdown was reversed by SDHD depletion. MBD1 recruited DNMT1 to enhance SDHD promoter methylation and suppress its expression, thereby inducing mitochondrial dysfunction in trophoblast cells and ultimately promoting PE progression.<\/jats:p>","DOI":"10.1096\/fj.202601983r","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:38:34Z","timestamp":1787236714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MBD1<\/scp>\n                    \u2010Mediated\n                    <scp>SDHD<\/scp>\n                    Methylation Aggravates Preeclampsia Progression via Triggering Mitochondrial Dysfunction"],"prefix":"10.1096","volume":"40","author":[{"given":"Shaoping","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology The Fourth Hospital of Changsha (Integrated Traditional Chinese and Western Medicine Hospital of Changsha, Changsha Hospital of Hunan Normal University)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Fourth Hospital of Changsha (Integrated Traditional Chinese and Western Medicine Hospital of Changsha, Changsha Hospital of Hunan Normal University)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Fourth Hospital of Changsha (Integrated Traditional Chinese and Western Medicine Hospital of Changsha, Changsha Hospital of Hunan Normal University)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2815-4883","authenticated-orcid":false,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Fourth Hospital of 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