{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:12:05Z","timestamp":1776773525852,"version":"3.51.2"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>This article aims to investigate the possible mechanism by which nuclear factor erythroid 2\u2010related factor 2 (Nrf2) signaling exerts protective effects on the progression of preeclampsia (PE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HTR\u20108\/SVneo cells were cultured under hypoxic conditions to establish PE cell model. Cell viability and invasion were respectively examined by CCK\u20108 assay and transwell assay. The detection of oxidative stress and Fe<jats:sup>2+<\/jats:sup> content was carried out by corresponding commercial kits, and the expression of corresponding proteins and genes was detected by western blot and qPCR. After Nrf2 was overexpressed in HTR\u20108\/SVneo cells, the above assays were conducted to confirm the exact effects of Nrf2 activation on ferroptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypoxia reduced the invasion of HTR\u20108\/SVneo cells, induced oxidative stress (upregulated levels of glutathione [GSH], malondialdehyde [MDA], and reactive oxygen species [ROS]), and induced ferroptosis which exhibited by upregulated Fe<jats:sup>2+<\/jats:sup> and downregulated expression of solute carrier family 7 member 11\/System xCT (SCL7A11), glutathione peroxidase 4 (GPX4), and ferroportin1 (FPN1). Meanwhile, hypoxia promoted the translocation of Nrf2 to the nucleus, leading to Nrf2\/HO\u20101 signaling activation. These changes upon hypoxia induction were strengthened by ferric ammonium citrate (FAC) but were abolished by deferoxamine (DFO). Moreover, Nrf2 overexpression in hypoxia\u2010induced HTR\u20108\/SVneo cells exerted inhibitory effects on levels of GSH, MDA, ROS, and Fe<jats:sup>2+<\/jats:sup>, and promotive effects on Nrf2\/HO\u20101 signaling activation and expression of SCL7A11, GPX4, and FPN1, indicating that Nrf2 overexpression decreased oxidative stress and ferroptosis in hypoxia\u2010induced HTR\u20108\/SVneo cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, activation of Nrf2 signaling alleviated hypoxia\u2010induced invasion lacking, oxidative stress, and ferroptosis in hypoxia\u2010induced HTR\u20108\/SVneo cells, suggesting that Nrf2 signaling activation play a protective role in PE, which can provide instructions for the targeted treatment of PE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jog.15009","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T23:15:24Z","timestamp":1631747724000},"page":"3797-3806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Activation of Nrf2 signaling protects hypoxia\u2010induced <scp>HTR<\/scp>\u20108\/<scp>SVneo<\/scp> cells against ferroptosis"],"prefix":"10.1111","volume":"47","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province  Wuhan City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province  Wuhan City 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