Maternal Bisphenol A Exposure Induces Hippocampal‐Dependent Learning and Memory Deficits Through the PI3K/Akt/mTOR Pathway in Male Offspring Rats

ABSTRACT Bisphenol A (BPA), an environmental endocrine disrupting chemical, is one of the most widely used chemicals in the world and is widely distributed in the external environment, specifically in food, water, dust, and soil. BPA exposure is associated with abnormal cognitive behaviors. However, the underlying mechanism remains unclear. In this study, pregnant female Sprague Dawley rats were orally exposed to BPA at a low dose of 0, 0.04, 0.4, or 4 mg per kg·of body weight per day from embryonic Day 0 (ED 0) to postnatal Day 21 (PND 21). Spatial learning and memory were measured via a Morris water maze test on PND 22. PI3K/Akt/mTOR signaling pathway protein expression was detected in the hippocampi of male offspring using a western blot. The water maze test demonstrated that BPA exposure considerably reduced the learning and memory capacities of the male offspring exposure groups when compared to the control group. The male offspring rats' latency to escape increased significantly, the time taken to traverse a platform reduced, and latency to find a hidden platform showed an increasing trend. Meanwhile, maternal exposure to BPA downregulated the expression of PI3K/Akt/mTOR/p70S6K pathway in the hippocampi of the offspring. Moreover, BPA exposure improved the GSK3β and phosphorylated tau protein (T231) levels, increased malondialdehyde levels, and activated caspase‐3 expression in the hippocampi of the male offspring rats. Taken together, these findings indicate that maternal exposure to BPA causes learning and memory impairment and that the PI3K/Akt/mTOR pathway participates in the mechanism of BPA‐induced neurocognitive decline.