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Intrauterine inflammation is an etiological factor that drives PTB, and oxidative stress is associated with PTB. Nuclear erythroid 2-related factor 2 (<jats:italic>Nrf2<\/jats:italic>) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and inflammatory stress. Here, we used the established mouse model of intrauterine inflammation-induced PTB to determine whether Nrf2 is a modifier of susceptibility to PTB and prematurity-related morbidity and mortality in the offspring. We determined that Nr2-deficient (Nrf2<jats:sup>\u2212\/\u2212<\/jats:sup>) mice exhibited a greater sensitivity to intrauterine inflammation, as indicated by decreased time to delivery, reduced birthweight, and 100% mortality. Placentas from preterm Nrf2<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed elevated levels of markers of inflammation, oxidative stress, and cell death, and transcriptomic analysis identified numerous key signaling pathways that were differentially expressed between wild-type (WT) and Nrf2<jats:sup>\u2212\/\u2212<\/jats:sup> mice in both preterm and control samples. Thus, Nrf2 could be a critical factor for gene-environment interactions that may determine susceptibility to PTB. Further studies are needed to determine if Nrf2 is a viable therapeutic target in women who are at risk for PTB and associated complications in the affected offspring.<\/jats:p>","DOI":"10.1038\/srep40194","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T10:46:47Z","timestamp":1484045207000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Nrf2 regulates gene-environment interactions in an animal model of intrauterine inflammation: Implications for preterm birth and prematurity"],"prefix":"10.1038","volume":"7","author":[{"given":"Thomas E.","family":"Sussan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuladeep","family":"Sudini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"C. 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