{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:15:36Z","timestamp":1777457736159,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cleft palate is a congenital malformation influenced by both genetic and environmental factors. Although environmental contributors have been extensively studied, the placenta\u2014an essential organ that mediates maternal\u2013fetal interactions and offers protection against environmental insults\u2014remains poorly understood in this context. This study aimed to explore transcriptomic and metabolomic alterations in the placenta following maternal exposure to corticosteroids, using a dexamethasone\u2010induced cleft palate rabbit model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Untargeted metabolomics and transcriptomics analyses were conducted on placental and amniotic fluid samples from fetuses with and without dexamethasone\u2010induced cleft palate. Histopathological examination was performed to assess structural abnormalities in the placenta.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cleft palate group exhibited marked placental pathologies, including fibrosis, calcification, and necrosis. Transcriptomic analysis identified 4744 differentially expressed genes, enriched in pathways related to hormone signaling, vascular development, and inflammation. Metabolomic profiling revealed significant changes in both placenta and amniotic fluid, especially in the urea cycle, aspartate metabolism, and nicotinate and nicotinamide metabolism. The urea cycle was particularly disrupted in the cleft palate group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings reveal a strong association between placental structural and functional abnormalities and cleft palate formation in the dexamethasone\u2010induced model, offering novel insights into the potential role of the placenta in cleft palate pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2467","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T14:19:33Z","timestamp":1743430773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Transcriptomic and Metabolomic Profiling of the Placenta in a Dexamethasone\u2010Induced Cleft Palate Rabbit Model"],"prefix":"10.1002","volume":"117","author":[{"given":"Lanling","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; 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