Chronic exposure of bisphenol-A impairs cognitive function and disrupts hippocampal insulin signaling pathway in male mice

Bisphenol-A (BPA), a well-known estrogenic endocrine disruptor, is generally applied to turn out plastic consumer products. Available data have manifested that exposure to BPA can trigger insulin resistance. Hence, the purpose of the actual study was to consider the impacts of BPA exposure on cognitive function and insulin signaling pathway in the hippocampus of male offspring mice. For this purpose, the pregnant female mice were treated either vehicle (0.1% ethanol) or BPA (0.01, 0.1, and 1 µg/mL) via drinking water from day 1 of gestation until delactation (D1-PND21, newborn exposure). Afterward, the three-week-old male offspring mice took orally with the same doses of BPA for nine weeks (PND84). The behavioral tests, blood sugar level, histological observation, transcriptome sequencing, glucose transporter 4 (GLUT4), and hippocampal insulin signaling pathway were checked for the male offspring mice at 13 weeks of age (PND91). Our data indicated that BPA exposure impaired cognitive function, disrupted the hippocampal regular cell arrangement, increased blood glucose levels, disturbed the insulin signaling pathway including phosphorylated insulin receptor substrate1 (p-IRS1), protein kinase B (p-AKT), and glycogen synthase kinase 3β (p-GSK3β). At the same time, the mRNA and protein expressions of GLUT4 were markedly down-regulated in the BPA-exposed groups. To sum up, it has been suggested from these results that BPA has detrimental effects on the insulin signaling pathway, which might subsequently be conducive to the impairment of cognitive function in the adult male offspring mice. Therefore, BPA exposure might in part be an element of risk for the long-term neurodegeneration in male offspring mice. •BPA decreased cognitive function of F1-male mice.•Blood sugar levels of F1-male mice were obviously increased after thirteen weeks treated with BPA.•BPA inhibited the protein and mRNA expressions of the insulin signaling pathway and GLUT4 in the hippocampus.