{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:27:04Z","timestamp":1789680424874,"version":"4.0.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Our objective was to determine the role of toll-like receptor 4 (TLR4) in uterine ischemia\/reperfusion (I\/R)-induced fetal growth restriction (FGR). Pregnant TLR4-deficient and wild-type mice were subjected to I\/R or a sham procedure. Fetal and placental weights were recorded and tissues were collected. Pep-1 (inhibits low-molecular-weight hyaluronan (LMW-HA) binding to TLR4) was used to determine whether LMW-HA\u2013TLR4 interaction has a role in FGR. TLR4-deficient mice exhibited significantly lower baseline fetal weights compared with wild-type mice (P&amp;lt;0.05), along with extensive placental calcification that was not present in wild-type mice. Following I\/R, fetal and placental weights were significantly reduced in wild-type (P&amp;lt;0.05) but not in TLR4-deficient mice. However, I\/R increased fetal loss (P&amp;lt;0.05) only in TLR4-deficient mice. Corresponding with the reduced fetal weights, uterine myeloperoxidase activity increased in wild-type mice (P&amp;lt;0.001), indicating an inflammatory response, which was absent in TLR4-deficient mice. TLR4 was shown to have a regulatory role for two anti-inflammatory cytokines: interferon-B1 decreased only in wild-type mice (P&amp;lt;0.01) and interleukin-10 increased only in TLR4-deficient mice (P&amp;lt;0.001), in response to I\/R. Pep-1 completely prevented I\/R-induced FGR (P&amp;lt;0.001), indicating a potential role for the endogenous TLR4 ligand LMW-HA in I\/R-induced FGR. In conclusion, uterine I\/R in pregnancy produces FGR that is dependent on TLR4 and endogenous ligand(s), including breakdown products of HA. In addition, TLR4 may play a role in preventing pregnancy loss after uterine I\/R.<\/jats:p>","DOI":"10.1530\/rep-12-0433","type":"journal-article","created":{"date-parts":[[2013,3,19]],"date-time":"2013-03-19T00:03:00Z","timestamp":1363651380000},"page":"517-526","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":7,"title":["Impact of toll-like receptor 4 deficiency on the response to uterine ischemia\/reperfusion in mice"],"prefix":"10.1093","volume":"145","author":[{"given":"Larry G","family":"Thaete","sequence":"first","affiliation":[{"name":"Departments of Obstetrics and Gynecology 2 Pediatrics 3 \u00a0 NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen #1507, Evanston, Illinois 60201, USA 4 \u00a0 The University of Chicago, Chicago, Illinois, USA"},{"name":"Surgery and Pathology 2 Pediatrics 3 \u00a0 NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen #1507, Evanston, Illinois 60201, USA 4 \u00a0 The University of Chicago, Chicago, Illinois, USA"},{"name":"Pritzker School of Medicine 2 Pediatrics 3 \u00a0 NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen #1507, Evanston, Illinois 60201, USA 4 \u00a0 The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wu","family":"Qu","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology 2 Pediatrics 3 \u00a0 NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen #1507, Evanston, Illinois 60201, USA 4 \u00a0 The University of Chicago, Chicago, Illinois, USA"},{"name":"Surgery and Pathology 2 Pediatrics 3 \u00a0 NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen #1507, Evanston, Illinois 60201, USA 4 \u00a0 The University of Chicago, Chicago, Illinois, USA"},{"name":"Pritzker School of Medicine 2 Pediatrics 3 \u00a0 NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen #1507, Evanston, Illinois 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