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The mildly hypertensive BPH\/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal\/fetal interface leads to elevation in local TNF-\u03b1 levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-\u03b1 improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.<\/jats:p>","DOI":"10.4049\/jimmunol.1402220","type":"journal-article","created":{"date-parts":[[2015,6,13]],"date-time":"2015-06-13T03:40:47Z","timestamp":1434166847000},"page":"1129-1138","source":"Crossref","is-referenced-by-count":86,"title":["Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency"],"prefix":"10.1093","volume":"195","author":[{"given":"Shari E","family":"Gelber","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Weill Cornell Medical Center , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyssa","family":"Brent","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Weill Cornell Medical Center , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Redecha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hospital for Special Surgery, Weill Cornell Medical Center , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Perino","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Hospital for Special Surgery , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Darby Children\u2019s Research Institute, Medical University of South Carolina , Charleston, SC 29425"},{"name":"Ralph H. Johnson Veterans Affairs Medical Center , Charleston, SC 29401"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L","family":"Davisson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853"},{"name":"Department of Cell and Developmental Biology, Weill Cornell Medical Center , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E","family":"Salmon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hospital for Special Surgery, Weill Cornell Medical Center , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703543123500_r1","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1136\/jcp.2008.055236","article-title":"The placenta in pre-eclampsia and intrauterine growth restriction","volume":"61","author":"Roberts","year":"2008","journal-title":"J. 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