Maternal Large Yellow Tea Supplementation Confers Intergenerational Protection Against BPA-Induced Metabolic and Behavioral Disorders in Mice

Background: Large yellow tea (LYT), a distinctive variety made from mature leaves, has recently gained attention for its remarkable health benefits. However, whether these benefits can be transmitted from mother to offspring remains unexplored. Purpose: This study investigated whether maternal LYT consumption confers intergenerational protection against metabolic and behavioral disorders induced by perinatal bisphenol A (BPA) exposure in F1 offspring. Methods: A mouse model of perinatal BPA exposure (0.03% in diet) was established with or without maternal LYT supplementation (2.5% in diet). Metabolic parameters were assessed through biochemical assays and gene expression analysis (RT-PCR). Energy expenditure and spontaneous activity were monitored using a Comprehensive Lab Animal Monitoring System (CLAMS). Hippocampal proteomic profiling was performed using label-free quantitative proteomics. Results: LYT significantly reduced maternal BPA body burden, potentially via limiting absorption, enhancing glucuronidation metabolism, and promoting excretion. Notably, LYT exhibited bidirectional metabolic regulation, alleviating gestational hyperglycemia in dams while restoring hypoglycemia in offspring, and normalizing underweight and hypolipidemia. Mechanistically, the SIRT6 (sirtuin 6)/FOXO1 and SIRT6/SREBP1 pathways may be involved in regulating gluconeogenesis and lipogenesis. Concurrently, LYT rectified BPA-induced hyperactivity and reduced excessive energy expenditure. Proteomic analysis revealed that LYT partially restores BPA-induced dysregulation of cholesterol metabolism and glutamatergic/GABAergic synaptic pathways, which may contribute to rebalancing synaptic homeostasis. Conclusions: These findings suggest that maternal LYT supplementation confers intergenerational protection against BPA-induced metabolic and behavioral disorders in mice, potentially acting through enhanced toxin clearance, bidirectional metabolic regulation, behavioral normalization, and partial restoration of hippocampal synaptic homeostasis. This study provides a theoretical basis for developing natural dietary interventions to mitigate developmental toxicant-induced health risks.