{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:25Z","timestamp":1791974125162,"version":"4.4.0"},"reference-count":48,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gynecol Obstet Invest"],"abstract":"<jats:p>Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H&lt;sub&gt;2&lt;\/sub&gt;S) can inhibit necroptosis of human umbilical vein endothelial cells under the high glucose-induced injury. Whether H&lt;sub&gt;2&lt;\/sub&gt;S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study aimed to explore the protective role of H&lt;sub&gt;2&lt;\/sub&gt;S in trophoblast cells against necroptosis underlying PE. Design: This is an in vitro experimental study. Participants: A total of 10 pregnant women with severe PE and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. Methods: The expression and localization of necrotic proteins were assayed in human placenta samples, and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H&lt;sub&gt;2&lt;\/sub&gt;S donor) and SB203580 (p38 inhibitor). Results: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine \u03b2-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. Limitations: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of PE. Conclusions: We proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8\/3 and increased expression of RIPA1 and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H&lt;sub&gt;2&lt;\/sub&gt;S protected cytotrophoblasts against ceramide-induced necroptosis via the p38MAPK pathway. <\/jats:p>","DOI":"10.1159\/000538261","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T21:00:34Z","timestamp":1713387634000},"page":"387-401","source":"Crossref","is-referenced-by-count":8,"title":["Exogenous Hydrogen Sulfide Prevents Necroptosis by Inhibiting p38MAPK Pathway Activation in JEG-3 Trophoblast Cells: A Role in 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