{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:00:42Z","timestamp":1790352042145,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Graz; Austrian Science Fund"},{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Placental growth is most rapid during the first trimester (FT) of pregnancy, making it vulnerable to metabolic and endocrine influences. Obesity, with its inflammatory and oxidative stress, can cause cellular damage. We hypothesized that maternal obesity increases DNA damage in the FT placenta, affecting DNA damage response and trophoblast turnover. Examining placental tissue from lean and obese non-smoking women (4\u201312 gestational weeks), we observed higher overall DNA damage in obesity (COMET assay). Specifically, DNA double-strand breaks were found in villous cytotrophoblasts (vCTB; semi-quantitative \u03b3H2AX immunostaining), while oxidative DNA modifications (8-hydroxydeoxyguanosine; FPG-COMET assay) were absent. Increased DNA damage in obese FT placentas did not correlate with enhanced DNA damage sensing and repair. Indeed, obesity led to reduced expression of multiple DNA repair genes (mRNA array), which were further shown to be influenced by inflammation through in vitro experiments using tumor necrosis factor-\u03b1 treatment on FT chorionic villous explants. Tissue changes included elevated vCTB apoptosis (TUNEL assay; caspase-cleaved cytokeratin 18), but unchanged senescence (p16) and reduced proliferation (Ki67) of vCTB, the main driver of FT placental growth. Overall, obesity is linked to heightened non-oxidative DNA damage in FT placentas, negatively affecting trophoblast growth and potentially leading to temporary reduction in early fetal growth.<\/jats:p>","DOI":"10.1093\/molehr\/gaae027","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T13:30:19Z","timestamp":1722605419000},"source":"Crossref","is-referenced-by-count":6,"title":["Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas"],"prefix":"10.1093","volume":"30","author":[{"given":"Denise","family":"Hoch","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Medical University of Graz , Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Majali-Martinez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Medical University of Graz , Graz, Austria"},{"name":"Departamento de 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