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Reduced expression of mitochondrial dihydroorotate dehydrogenase (DHODH) was observed in early\u2010onset HDP placentas in our previous study. Experiments using human trophoblast stem cells demonstrated that DHODH inhibition impairs syncytialization and induces cellular senescence via mitochondrial and endoplasmic reticulum stress, elevating sFlt1\/PlGF levels, a hallmark of placental dysfunction in HDPs. Mitochondrial activators quercetin and riboflavin partially reversed these effects. Our findings suggest that DHODH may be a key regulator of trophoblast differentiation by linking organelle stress to cellular senescence.<\/jats:p>","DOI":"10.1002\/2211-5463.70194","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:52:28Z","timestamp":1768564348000},"page":"1166-1180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dihydroorotate dehydrogenase (\n                    <scp>DHODH<\/scp>\n                    ) regulates trophoblast syncytialization through organelle stress\u2013induced cellular senescence"],"prefix":"10.1002","volume":"16","author":[{"given":"Kanoko","family":"Yoshida","sequence":"first","affiliation":[{"name":"Laboratory of Endocrine Pharmacology Tokyo University of Pharmacy and Life Sciences  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