{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:10:11Z","timestamp":1791774611678,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study aimed to investigate the role of STOX1 in trophoblast pyroptosis during preeclampsia (PE) and elucidate its underlying molecular mechanisms. A trophoblast hypoxia cell model was established by exposing HTR\u20108\/SVneo cells to hypoxic conditions. The results showed that STOX1 messenger RNA expression was significantly elevated in placental tissues from PE patients as well as in hypoxia\u2010treated HTR\u20108\/SVneo cells. Hypoxia markedly induced pyroptosis in HTR\u20108\/SVneo cells, whereas STOX1 silencing enhanced cell proliferation and migration while suppressing programmed cell death. Moreover, STOX1 knockdown reduced the levels of reactive oxygen species and malondialdehyde, increased superoxide dismutase (SOD) activity, and decreased the expression of pyroptosis\u2010associated inflammatory cytokines, including interleukin\u20101\u03b2 (IL\u20101\u03b2) and interleukin\u201018 (IL\u201018). In addition, silencing STOX1 downregulated the expression of inflammasome\u2010related proteins, including NLRP3, ASC, cleaved caspase\u20101, and GSDMD\u2010N. Mechanistically, STOX1 knockdown activated the Nrf2\/HO\u20101 signaling pathway, as evidenced by increased expression of Nrf2 and HO\u20101 and decreased expression of Keap1. Rescue experiments further demonstrated that co\u2010silencing Nrf2 partially reversed the inhibitory effects of STOX1 knockdown on pyroptosis in hypoxia\u2010treated HTR\u20108\/SVneo cells. Collectively, these findings indicate that STOX1 is upregulated in PE and that STOX1 silencing alleviates oxidative stress and inhibits caspase\u20101\u2010mediated trophoblast pyroptosis through activation of the Nrf2 signaling pathway. Consequently, STOX1 may serve as a promising therapeutic target for the prevention and treatment of preeclampsia.<\/jats:p>","DOI":"10.1002\/mrd.70145","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:44:46Z","timestamp":1788439486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["STOX1 Promotes Pyroptosis of Hypoxic Trophoblast Cells Via the Nrf2\/Caspase\u20101 Axis"],"prefix":"10.1002","volume":"93","author":[{"given":"Huiqiu","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics The Second Affiliated Hospital of Wenzhou Medical University Wenzhou 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