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We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The injury model was established by treating JEG3 cells with hypoxia for 24\u00a0h. The functional measurements were assessed by the cell counting kit\u20108, propidium iodide (PI)\/Annexin V staining, JC\u20101 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot. PGAM5 was knocked down to study its role in hypoxia\u2010induced necroptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The placentae from patients with preeclampsia showed up\u2010regulation of PGAM5 and decreased levels of p\u2010Drp1\u2010S637, accompanied by increased necroptosis\u2010relevant proteins expression. The expression of PGAM5 in JEG3 cells was up\u2010regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI<jats:sup>+<\/jats:sup>\/Annexin V<jats:sup>+<\/jats:sup> cells and decreased cell viability), accompanied by increased expression of necroptosis\u2010relevant proteins; knockdown of PGAM5 attenuated these phenomena.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13539","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T07:09:04Z","timestamp":1647673744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phosphoglycerate mutase 5 promotes necroptosis in trophoblast cells through activation of dynamin\u2010related protein 1 in early\u2010onset preeclampsia"],"prefix":"10.1111","volume":"87","author":[{"given":"Jiejie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Early Life Development and Disease Prevention  Changsha 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