{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:14:39Z","timestamp":1791976479775,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Preeclampsia (PE)\u00a0is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells\u2010trophoblasts. Phenylbutyric acid (4\u2010PBA), an ERS inhibitor, is involved in regulating the development of ERS\u2010related diseases. At present, how 4\u2010PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR\u20108\/SVneo cells with hypoxia. To verify the underlying mechanisms of 4\u2010PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4\u2010PBA restored hypoxia\u2010induced trophoblast viability, inhibited HIF\u20101\u03b1 protein expression, inflammation, and PERK\/ATF\u20104\/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4\u2010PBA decreased hypoxia\u2010induced apoptosis in trophoblasts. The results of the JC\u20101 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4\u2010PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin\u20101, LC3II, and decreased p62 were seen in hypoxia\u2010stimulated cells. These changes were reversed by 4\u2010PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4\u2010PBA on the viability, apoptosis, and autophagosome number of hypoxia\u2010induced trophoblasts. In summary, 4\u2010PBA reduces autophagy and apoptosis via the PERK\/ATF\u20104\/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4\u2010PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.<\/jats:p>","DOI":"10.1002\/mrd.23742","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T03:03:45Z","timestamp":1713755025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phenylbutyric acid inhibits hypoxia\u2010induced trophoblast apoptosis and autophagy in preeclampsia\u00a0via the PERK\/ATF\u20104\/CHOP pathway"],"prefix":"10.1002","volume":"91","author":[{"given":"Yinfeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of ICU Jiaxing Maternity and Children Health Care Hospital Jiaxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of ICU Jiaxing Maternity and Children Health 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