Bisphenol a exposure decreases learning ability through the suppression of mitochondrial oxidative phosphorylation in the hippocampus of male mice.

Bisphenol-A (BPA) is ubiquitous in the environment. Many studies have demonstrated that BPA triggers central nervous system dysfunction in animals, however, the molecular mechanisms of BPA neurotoxicity are unclear. Hence, this study aimed to evaluate the neurotoxic effects of male mouse hippocampus under BPA exposure (0 mg/L, control group (C); 0.01 mg/L, low dose (L); 0.1 mg/L, medium dose (M); and 1 mg/L, high dose (H)). Nine differentially expressed genes (DEG) related to oxidative phosphorylation (OXPHOs) were screened out and located through an interaction network and co-enrichment analysis. Overall, BPA exposure disrupted the regular cell arrangement in the hippocampus, reduced learning abilities and the ratio of testosterone (T)/estradiol (E2), inhibited gene expressions concerned OXPHOs, especially reduced protein expression level of the Ndufb10 related to learning ability and the activities of complex I, III, IV, and Ⅴ, which ultimately caused abnormal ATP synthesis of hippocampal mitochondria and led to shrinking rapidly myocardial energy supply in the brain (hippocampus). These results indicated that the destruction of mitochondrial OXPHOs might be one of the mechanisms of BPA-induced learning ability decline in mice. In conclusion, our results provide a creative understanding and research direction for the molecular alterations and signal pathways of BPA-induced neurotoxicity.