{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:29:06Z","timestamp":1789946946358,"version":"4.0.1"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,6,17]],"date-time":"2018-06-17T00:00:00Z","timestamp":1529193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD084532\u201001A1"],"award-info":[{"award-number":["1R01HD084532\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Problem<\/jats:title><jats:p>Oxidative stress (OS)\u2010induced, p38 mitogen\u2010activated protein kinase (p38MAPK)\u2010mediated chorioamniotic senescence and inflammation (senescence\u2010associated secretory phenotype [SASP]) are associated with parturition. In response to OS\u2010inducing risk factors, premature senescence contributes to preterm premature rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). We determined the effect of simvastatin, rosuvastatin, and progesterone in downregulating p38MAPK\u2010mediated senescence and SASP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Normal term, not\u2010in\u2010labor fetal membranes (n\u00a0=\u00a08) were exposed to cigarette smoke extract (CSE: OS inducer) alone or combined with simvastatin (100 and 200\u00a0ng\/mL), rosuvastatin (100 and 200\u00a0ng\/mL), and progesterone (10<jats:sup>\u22126<\/jats:sup>\u00a0mol\/L). p38MAPK expression changes were studied by Western blot, senescence was determined by senescence\u2010associated \u03b2\u2010Galactosidase (SA\u2010\u03b2\u2010Gal) staining, and multiplex analysis determined changes associated with 4 SASP markers (IL\u20108, IL\u201010, TNF\u2010\u03b1, and GM\u2010CSF). A pairwise comparison between groups was conducted by ANOVA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to untreated controls, CSE induced p38MAPK\u2010mediated senescence and SASP. CSE cotreatment with simvastatin and rosuvastatin significantly reduced p38MAPK activation, senescence (decrease in SA\u2010\u03b2\u2010Gal) and SASP markers, GM\u2010CSF, and TNF, but not IL\u20108, while increasing anti\u2010inflammatory IL\u201010 in a dose\u2010dependent manner. Cotreatment of CSE and progesterone had no effect on reducing p38MAPK activation, senescence, or SASP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both simvastatin and rosuvastatin downregulated OS\u2010induced p38MAPK activation, senescence, and SASP, while rosuvastatin showed a pronounced effect. Progesterone did not reduce OS\u2010induced fetal membrane senescence and SASP. Simvastatin or rosuvastatin may reduce the incidences of OS\u2010associated PTB and pPROM by preventing premature senescence and SASP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12999","type":"journal-article","created":{"date-parts":[[2018,6,18]],"date-time":"2018-06-18T04:45:40Z","timestamp":1529297140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Regulation of p38 mitogen\u2010activated kinase\u2010mediated fetal membrane senescence by statins"],"prefix":"10.1111","volume":"80","author":[{"given":"Martina T.","family":"Ayad","sequence":"first","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology Division of Maternal\u2010Fetal Medicine &amp; Perinatal Research The University of Texas Medical Branch at Galveston  Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-1815","authenticated-orcid":false,"given":"Brandie 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