{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T16:24:42Z","timestamp":1781281482803,"version":"3.54.1"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Missed abortion is one of the common obstetrical and gynecological complications, angiogenesis is the most important factor in fetal and placental development. However, the definite etiology and pathogenesis are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mRNA levels of p53, MDM2, VEGF, and HIF\u2010l\u03b1 were detected in 60 villous samples of missed abortion patients and 64 healthy controls by quantitative reverse\u2010transcription polymerase chain reaction (qRT\u2010PCR). Immunohistochemistry was used to explore the expression and correlation of p53, MDM2, VEGF, and HIF\u2010l\u03b1 in villous tissues. Furthermore, we upregulated MDM2 expression in JEG\u20103 and BeWo cells under hypoxia, combined with Nutlin3, the cell cycle was determined using flow cytometry and the expressions of p53, MDM2, VEGF, and HIF\u20101\u03b1 were determined by qRT\u2010PCR and western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>qRT\u2010PCR demonstrated that the expressions of p53, MDM2, and HIF\u20101\u03b1 were significantly increased and VEGF was decreased in missed abortion group compared with normal pregnancies. Correlation analysis found that p53 was positively correlated with MDM2 and HIF\u20101\u03b1, and negatively correlated with VEGF in missed abortion group. After administration of Nutlin3, overexpression of MDM2 could arrest cell cycle in G1 phase and reduce the proportion of S phase. The expression of p53 and MDM2 of JEG\u20103 cells and BeWo cells which transfected with pcDNA3.1\u2010MDM2 plasmid were markedly increased after Nutlin3 addition under hypoxic conditions, while the expression of VEGF and HIF\u20101\u03b1 decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicated that during the development of villi in early pregnancy, p53\u2010MDM2 signaling regulate cell cycle and angiogenesis through interaction with HIF\u20101\u03b1 and VEGF, which may be a crucial factor affecting pregnancy outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jog.15385","type":"journal-article","created":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T05:35:31Z","timestamp":1659764131000},"page":"2686-2696","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The role of <scp>p53\u2010MDM2<\/scp> signaling in missed abortion and possible 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