Placental and Cleft Palate: Preliminary Insights from Integrated Metabolomic and Transcriptomic Analyses

Genetic and environmental factors contribute to the aetiology of clefts. Most major advances in the aetiology are the role of genes and pathways, few about environmental factors. Placenta, the key organ resisting to environmental factors, and yet, researchers know little about how it functions in fetal development, especially in birth defects like cleft palate. In this research, an analysis of untargeted metabolomics and transcriptomics was conducted to explore if there are obvious placental changes in maternal exposure to corticosteroid induced cleft palate, utilizing a dexamethasone-induced cleft palate rabbit model. Results show that, in cleft palate, obvious pathologic changes were observed in placenta including fibrosis, calcification, and necrosis. Transcriptomic analysis identified 4,744 differentially expressed genes in the placenta, involving pathways related to hormonal responses, vascular development, and inflammatory reactions. Metabolomics revealed significant metabolic differences in both the placenta and amniotic fluid including Urea Cycle, Aspartate Metabolism, Nicotinate and Nicotinamide Metabolism. Especially, Urea cycle is notably changed in placenta in maternal exposure to corticosteroid induced cleft palate. This offers a novel direction for studying environmental factors in birth defect, suggesting a potential role of placental functional disorders.