Bisphenols (BPs) can negatively affect neurobehaviors in rats, whereas the mechanism remains unclear. Here, the mechanism of BPs-induced neurodevelopmental toxicity and its effective detoxification measures were investigated in vitro and in vivo. In in vitro experiments, primary hippocampal neurons from neonatal rats of different genders were treated with bisphenol A (BPA), bisphenol S (BPS) and bisphenol B (BPB) at 1 nM-100 μM, epigallocatechin gallate (EGCG) and G15, an antagonist of G protein-coupled estrogen receptor (GPER) for 7 d. Results indicated that BPs affected neuronal morphogenesis, impaired GABA synthesis and Glu/GABA homeostasis. Neuronal morphogenetic damage induced by low-doses BPA may be mediated by GPER. Neurotoxicity of BPS is weaker than BPA and BPB. In in vivo studies, exposure to BPA (0.5 μg/kg·bw/day) on PND 10-40 caused oxidative stress and inflammation in rat hippocampus, disrupted neuronal morphogenesis and neurotransmitter homeostasis, ultimately impaired spatial memory of rats. Males are more sensitive to BPA exposure than females. Both in vivo and in vitro studies indicated that EGCG, a phytoestrogen, can alleviate BPA-induced neurotoxicity. Taken together, low-doses BPA exposure sex-specifically disrupted neurodevelopment and further impaired learning and memory ability in rats, which may be mediated by GPER. Promisingly, EGCG effectively mitigated the BPA-induced neurodevelopmental toxicity.
Keywords: Bisphenol A; EGCG; GPER; Information transmission; Neuronal morphogenesis.
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