{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:44:06Z","timestamp":1788997446909,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T00:00:00Z","timestamp":1569801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD076032"],"award-info":[{"award-number":["R01 HD076032"]}],"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":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Exposure to intrauterine inflammation (IUI) has been shown to induce fetal brain injury and increase the risk of acquiring a neurobehavioral disorder. The trafficking of the inflammatory mediator, lipopolysaccharide (LPS), in the pregnant female reproductive tract in the setting of IUI and the precise mechanisms by which inflammation induces fetal brain injury are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>FITC\u2010labeled LPS was utilized to induce IUI on E15, tissues were collected, and fluorescence was visualized via the Spectrum IVIS. Embryo transfer was utilized to create divergent maternal and fetal genotypes. Wild\u2010type (WT) embryos were transferred into TLR4\u2212\/\u2212 pseudopregnant dams (TLR4\u2212\/\u2212<jats:sub>mat<\/jats:sub>\/WT<jats:sub>fet<\/jats:sub>). On E15, TLR4\u2212\/\u2212<jats:sub>mat<\/jats:sub>\/WT<jats:sub>fet<\/jats:sub> dams or their WT controls (WT<jats:sub>mat<\/jats:sub>\/WT<jats:sub>fet<\/jats:sub>) received an intrauterine injection of LPS or phosphate\u2010buffered saline (PBS). Endotoxin and IL\u20106 levels were assessed in amniotic fluid, and cytokine expression was measured via QPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lipopolysaccharide trafficked to the uterus, fetal membranes, placenta, and the fetus and was undetectable in other tissues. Endotoxin was present in the amniotic fluid of all animals exposed to LPS. However, the immune response was blunted in TLR4\u2212\/\u2212<jats:sub>mat<\/jats:sub>\/WT<jats:sub>fet<\/jats:sub> compared with WT controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intrauterine administered LPS is capable of accessing the entire feto\u2010placental unit with or without a functional maternal TLR4. Thus, bacteria or bacterial byproducts in the uterus may negatively impact fetal development regardless of the maternal genotype or endotoxin response. Despite the blunted immune response in the TLR4\u2010deficient dams, an inflammatory response is still ignited in the amniotic cavity and may negatively impact the fetus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13189","type":"journal-article","created":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T14:03:50Z","timestamp":1567951430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The tracking of lipopolysaccharide through the feto\u2010maternal compartment and the involvement of maternal TLR4 in inflammation\u2010induced fetal brain injury"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5364-8287","authenticated-orcid":false,"given":"Amy G.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Maternal and Child Health Research Center Center for Research on Reproduction and Women's Health Perelman School of Medicine at 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for Research on Reproduction and Women's Health Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal A.","family":"Elovitz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Maternal and Child Health Research Center Center for Research on Reproduction and Women's Health Perelman School of Medicine at the University of Pennsylvania Philadelphia PA 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