{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:12:31Z","timestamp":1784045551615,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>\n                    Early-onset preeclampsia (EOPE) remains a leading cause of maternal and perinatal morbidity worldwide. This review synthesizes evidence that premature placental senescence, centered on syncytiotrophoblast stress and the senescence-associated secretory phenotype (SASP), provides a mechanistic framework connecting placental injury to the maternal syndrome. In EOPE, defective spiral artery remodeling (45) and repeated ischemia\u2013reperfusion can promote oxidative damage, persistent DNA-damage responses, impaired autophagy, and durable cell-cycle arrest in trophoblast lineages. Convergent data show elevated senescence markers (p16INK4a, p21, SA-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -galactosidase,\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -H2AX), transcriptomic signatures consistent with placental SASP programs, and senescent syncytiotrophoblast secretion\u2014PAI-1 (~4-fold) and activin A (~2-fold). The SASP can transform the placenta into a source of cytokines, antiangiogenic factors, cell-free nucleic acids, and extracellular vesicles that may bias the maternal circulation toward endothelial dysfunction. We propose a stage-based model of EOPE progression and discuss differences from late-onset disease. Senescence-linked circulating signals may support multimarker risk stratification and liquid-biopsy strategies. We emphasize that human causal evidence remains associative and the senescence model is best regarded as a testable framework complementing established immune, complement, and angiogenic models.\n                  <\/jats:p>","DOI":"10.3389\/fpubh.2026.1863387","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:00:54Z","timestamp":1784044854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Premature placental senescence in early-onset preeclampsia: syncytiotrophoblast SASP and the maternal syndrome"],"prefix":"10.3389","volume":"14","author":[{"given":"Meifang","family":"Zhou","sequence":"first","affiliation":[{"name":"Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihao","family":"Hong","sequence":"additional","affiliation":[{"name":"Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S0140-6736(20)32335-7","article-title":"Pre-eclampsia","volume":"398","author":"Chappell","year":"2021","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41572-023-00417-6","article-title":"Pre-eclampsia","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"S907","DOI":"10.1016\/j.ajog.2020.09.047","article-title":"Syncytiotrophoblast stress in preeclampsia: the convergence point for multiple pathways","volume":"226","author":"Redman","year":"2022","journal-title":"Am J Obstet Gynecol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"gaag001","DOI":"10.1093\/molehr\/gaag001","article-title":"Preeclampsia 2.0: 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