{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:56:49Z","timestamp":1775073409885,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Scholarship Council (CSC)","award":["202108130056"],"award-info":[{"award-number":["202108130056"]}]},{"name":"Open Access Publication Fund of the University of Duisburg-Essen, Essen, Germany","award":["202108130056"],"award-info":[{"award-number":["202108130056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The global spread of SARS-CoV-2 has increased infections among pregnant women. This study aimed to explore placental pathology alterations and angiogenic factor levels in term pregnant women after SARS-CoV-2 infection in a retrospective single-center study. Additionally, we investigated the role and underlying mechanism of the vascular inflammation-promoting, cysteine-rich protein 61 (CYR61\/CCN1) in this context. All analyses were performed in term pregnant women infected with or without SARS-CoV-2. The sFlt-1, PlGF, and sEng serum levels were quantified using ELISA. Placental protein expressions were examined by immunoblot and immunostaining. Additionally, the effect of CCN1 protein on SGHPL-5 trophoblast cells was examined. We found that SARS-CoV-2 activated the inflammatory response in pregnant women, leading to pronounced vascular alterations in placental villous tissues. Elevated serum anti-angiogenic factors (sFlt-1, sEng) upon SARS-CoV-2 infection may directly contribute to these pathological changes. Upregulated CCN1 and pNF-\u03baB in placental villous tissues of infected patients are identified as crucial factors in placental alterations. As a conclusion, CCN1 was significantly elevated in the placentas of term pregnant women infected with SARS-CoV-2. By activating a cascade of inflammatory responses, CCN1 induced the production of the anti-angiogenic factors sFlt-1 and sEng, which may lead to abnormal placental vascular architecture.<\/jats:p>","DOI":"10.3390\/cimb46040221","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T12:15:32Z","timestamp":1713442532000},"page":"3533-3550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CCN1-Mediated Signaling in Placental Villous Tissues after SARS-CoV-2 Infection in Term Pregnant Women: Implications for Dysregulated Angiogenesis"],"prefix":"10.3390","volume":"46","author":[{"given":"Yuyang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyan","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrix","family":"Reisch","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Kimmig","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-7027","authenticated-orcid":false,"given":"Antonella","family":"Iannaccone","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-4581","authenticated-orcid":false,"given":"Alexandra","family":"Gellhaus","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1056\/NEJMoa1709481","article-title":"Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas","volume":"378","author":"Hoen","year":"2018","journal-title":"N. 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