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In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia\u2013reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8\/SVneo cell lines.\u00a0PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues.\u00a0Similar to PE placentae, during OS induction, the\u00a0trophoblast\u00a0cells showed\u00a0altered invasion and migration properties with\u00a0significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, <jats:italic>N<\/jats:italic>-acetyl cysteine, thereby implying a ROS-specific effect and in the\u00a0trophoblast cells, OS triggers UPR pathway through IRE1\u03b1-XBP1 axis.\u00a0Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.<\/jats:p>","DOI":"10.1038\/s41598-021-97799-y","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T10:03:34Z","timestamp":1631786614000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway"],"prefix":"10.1038","volume":"11","author":[{"given":"Indrani","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby","family":"Dhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai Bhagwan","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapas Chandra","family":"Nag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asit Ranjan","family":"Mridha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parul","family":"Jaiswal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhrajit","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhradip","family":"Karmakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"97799_CR1","doi-asserted-by":"publisher","unstructured":"Aouache, R., Biquard, L., Vaiman, D. & Miralles, F. 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