{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:57:29Z","timestamp":1784901449429,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"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","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":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Estrogen (E2) is one of the main steroid hormones associated with pregnancy and parturition. High levels of E2 increase uterine contractions, promote fetal membrane weakening, and induce degradation of the cervical extracellular matrix (ECM). Current evidence supports the role of E2 in epithelial\u2010to\u2010mesenchymal transition (EMT) and inflammation in different cell types; however, its effects on the cellular components of the cervix are still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>In this study, we assessed the effects of gestational levels of E2 in: (a) the cellular transition of endocervical epithelial cells (EEC) and cervical stromal cells (CSC) in vitro using immunocytochemical staining and Western blot analyses for EMT markers (cytokeratin\u201018, E\u2010cadherin, N\u2010cadherin, SNAIL, and vimentin); (b) cell migration using in vitro scratch assays; (c) inflammatory cytokine (interleukin 1\u03b2 and TNF\u2010\u03b1) and MMP9 production under untreated and lipopolysaccharide (LPS)\u2010treated conditions using immunoassays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>E2 treatment and co\u2010treatment with LPS as a proxy for infection maintained the metastate of EEC (expression of both cytokeratin and vimentin) and the mesenchymal state of CSC. E2 delayed wound healing, which mimics the tissue remodeling process, in EEC and CSC. E2 led to persistently elevated levels of vimentin throughout the EEC wound healing process. E2 did not affect inflammatory cytokine production by EEC and CSC but increased MMP9 production by EEC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, these results show that third trimester levels of E2 may permit localized inflammation, increase MMP\u20109 production, and cause an EMT\u2010mediated impairment of the remodeling process in the cervix in vitro. These data suggest a potential contribution of E2 in cervical ripening.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13370","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T18:26:30Z","timestamp":1604600790000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effects of a gestational level of estradiol on cellular transition, migration, and inflammation in cervical epithelial and stromal cells"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4535-8837","authenticated-orcid":false,"given":"Ourlad Alzeus G.","family":"Tantengco","sequence":"first","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine and Perinatal Research Department of Obstetrics and Gynecology The University of Texas Medical Branch at Galveston Galveston TX USA"},{"name":"College of Medicine University of the Philippines Manila Manila 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