High-Fat Diet during Mouse Pregnancy Impairs Fetal Heart Development

Maternal overnutrition correlates with detrimental outcomes in offspring. However, the specific effects of gestational exposure to a high-fat diet (HFD) on fetal development remain unclear. This study aimed to elucidate the developmental phenotypes of neonatal organs and cardiomyocytes of mice exposed to gestational HFD, revealing growth retardation and a notable reduction in cardiomyocyte cell cycle activity. In this study, an HFD model was used to investigate the effects of maternal HFD on offspring development. Defective development was observed in the offspring, and severe restriction of cell proliferation was noted in the neonatal organs as a result of maternal HFD. Based on this evidence, we detected a reduction in cardiomyocyte proliferation in offspring exposed to maternal HFD. Moreover, RNA sequencing analysis revealed that HFD diminished fatty acid metabolism, enhanced the inflammatory response, and upregulated the transcription of genes involved in Tp53-regulated cell cycle arrest in postnatal day 0 (P0) cardiomyocytes. Furthermore, our results showed that the effects of the maternal diet during gestation are profound and normal lactation and feeding after delivery cannot help adult offspring recover from defective heart development. These findings highlight the diverse pathways affected by maternal HFD, particularly implicating a potential TP53-dependent mechanism contributing to cardiac defects in offspring.