{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:06:58Z","timestamp":1792390018712,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,4,15]],"date-time":"2018-04-15T00:00:00Z","timestamp":1523750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Placenta accreta is clinically associated with maternal uterine scar. Our objective was to investigate the biochemical contribution of maternal scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over\u2010invasion in placenta accreta is associated with aberrant invasion\u2010site signalling of growth and angiogenic factors known to be involved in wound healing and promotion of cell invasion through the epithelial to mesenchymal cellular programme.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Cross\u2010sectional series.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Yale\u2013New Haven Hospital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>Women with histologically confirmed normal and abnormal placentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Placental invasion site tissue sections were immunostained for endoglin and other angiogenic regulators, and transforming growth factor <jats:italic>\u03b2<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic>) proteins. Maternal serum endoglin, and the vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) mediators hypoxia\u2010inducible factor\u20101<jats:italic>\u03b1<\/jats:italic> (<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>1<jats:italic>\u03b1<\/jats:italic>) and endostatin, were assessed using immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>Differences in median H\u2010score by immunostaining and in mean serum level by immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By immunostaining, placenta accreta samples demonstrated intervillous endoglin shedding and increased trophoblast expression of its cleavage protein matrix metalloproteinase\u201014. Absent decidual <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>1<jats:italic>\u03b1<\/jats:italic> and endostatin were observed in areas of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> upregulation. <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic>1 was present in myocytes but not in collagen bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased in praevia and accreta when corrected for gestational age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Angiogenic and growth factors at the placental invasion site are altered in accreta, both by decidual absence and within myometrial scar. We postulate this promotes the invasive phenotype of placenta accreta by activating hyperinvasive trophoblast and by dysregulating placental vascular remodelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Funding<\/jats:title><jats:p>Yale Department of Obstetrics, Gynecology and Reproductive Sciences funds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable abstract<\/jats:title><jats:p>Placenta accreta histology shows dysregulation of angiogenic and growth factors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.15176","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T00:17:15Z","timestamp":1519345035000},"page":"1441-1448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Extravillous trophoblast invasion in placenta accreta is associated with differential local expression of angiogenic and growth factors: a\u00a0cross\u2010sectional study"],"prefix":"10.1111","volume":"125","author":[{"given":"CM","family":"Duzyj","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences Rutgers University Robert Wood Johnson School of Medicine New Brunswick NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"IA","family":"Buhimschi","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research Department of Pediatrics The Research Institute at Nationwide Children's Hospital The Ohio State University College of Medicine Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CA","family":"Laky","sequence":"additional","affiliation":[{"name":"Maternal Fetal Medicine Mary Washington Hospital Fredericksburg VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Cozzini","sequence":"additional","affiliation":[{"name":"Americorps Communities in Schools Central Texas Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research Department of Pediatrics The Research Institute at Nationwide Children's Hospital The Ohio State University College of Medicine Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Wehrum","sequence":"additional","affiliation":[{"name":"Maternal\u2010Fetal Care Center Florida Hospital Medical Group Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CS","family":"Buhimschi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; 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