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

Abstract

The correlation between glucocorticoids and cleft palate, a prevalent congenital abnormality, remains controversial, particularly concerning the uncertain status of placenta-palate formation. Utilizing a dexamethasone-induced cleft palate model in New Zealand rabbits, an integrated analysis of untargeted metabolomics and transcriptomics was conducted to explore the correlation between placental pathology and cleft palate. After dexamethasone treatment, approximately 60% of rabbit embryos developed cleft palates. Obvious pathologic change were observed on 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. Metabolomic data revealed significant metabolic differences in both the placenta and amniotic fluid, with notable increases in urea levels in the placenta, while urea and arginine levels were markedly reduced in the amniotic fluid. Furthermore, metabolic disruptions in urea cycle, particularly an increase in arginase activity, may related to placental pathological changes. Overall, there is a correlation between placental pathology and cleft palate. Disruption of the urea cycle may contribute to placental lesions associated with the development of cleft palate. This offers a novel direction for understanding the mechanism of cleft palate formation, suggesting a potential significant role of placental metabolic disorders.