{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T08:43:51Z","timestamp":1768639431232,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"content-version":"am","delay-in-days":352,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006831","name":"U.S. Air Force","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006831","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010460","name":"U.S. Army Medical Command","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010460","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":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Protective effects for adult neurological disorders have been attributed to sex hormones. Using a murine model of prematurity, we evaluated the role of estrogen signaling in the process of perinatal brain injury following exposure to intrauterine inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>Intrauterine lipopolysaccharide (LPS) was used to invoke preterm labor and fetal neuroinflammation. Fetal brains were analyzed for changes in <jats:italic>Esr1, Esr2<\/jats:italic> and <jats:italic>Cyp19<\/jats:italic>. Dams heterozygous for the <jats:italic>Esr1<\/jats:italic> knockout allele were also given intrauterine LPS to compare delivery and offspring viability to wild type controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The upregulation in inflammatory cytokines was accompanied by an increase in <jats:italic>Esr1<\/jats:italic> and <jats:italic>Esr2<\/jats:italic> transcripts, though protein levels declined. <jats:italic>Cyp19<\/jats:italic> did not differ by mRNA or protein abundance. Offspring from <jats:italic>Esr1<\/jats:italic> mutants were larger, had a longer gestation and significantly greater mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Estrogen signaling is altered in the fetal brains of preterm offspring exposed to neuroinflammatory injury. The reduction of Esr1 and Esr2 proteins with LPS suggests that these proteins are degraded. It is possible that transcriptional upregulation of <jats:italic>Esr1<\/jats:italic> and <jats:italic>Esr2<\/jats:italic> occurs to compensate for the loss of these proteins. Alternatively, the translation of <jats:italic>Esr1<\/jats:italic> and <jats:italic>Esr2<\/jats:italic> mRNAs may be disrupted with LPS while a feedback mechanism upregulates transcription. Intact <jats:italic>Esr1<\/jats:italic> signaling is also associated with early preterm delivery following exposure to intrauterine LPS. A loss of one <jats:italic>Esr1<\/jats:italic> allele delays this process, but appears to do so at the cost of fetal viability. These results suggest estrogen signaling plays opposing roles between maternal and fetal responses to preterm birth.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13662","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T10:02:41Z","timestamp":1669975361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Estrogen receptor 1 appears essential for fetal viability in a murine model of premature birth"],"prefix":"10.1111","volume":"89","author":[{"given":"Stacey S.","family":"Schmiedecke","sequence":"first","affiliation":[{"name":"Division of Maternal Fetal Medicine Madigan Army Medical Center  Tacoma Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-7361","authenticated-orcid":false,"given":"Andrew S.","family":"Thagard","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine Madigan Army 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