Perinatal low-dose bisphenol AF exposure impairs synaptic plasticity and cognitive function of adult offspring in a sex-dependent manner

Bisphenol AF (BPAF), a kind of the ideal substitutes of Bisphenol A (BPA), has frequently been detected in environmental media and biological samples. Numerous studies have focused on the reproductive toxicity, cardiotoxicity and endocrine disrupting toxicity of BPAF. However, little evidence is available on neurodevelopmental toxicity of BPAF. Here, our study is to evaluate the effect of perinatal BPAF exposure (0, 0.34, 3.4 and 34 mg/kg body weight/day, correspond to Ctrl, low-, medium- and high-dose groups) on the cognitive function of adult mouse offspring. This study firstly found that perinatal BPAF exposure caused cognitive impairments of mouse offspring, in which male offspring was more sensitive than female offspring in low- and medium-dose BPAF groups. Furthermore, the dendritic arborization and complexity of hippocampal CA1 and DG neurons in male offspring were impaired in all BPAF groups, and these effects were only found in highdose BPAF group for female offspring. The damage of BPAF to dendritic spines, and the structural basis of learning and memory, was found in male offspring but not in females. Correspondingly, perinatal BPAF exposure significantly downregulated the expressions of hippocampal PSD-95 and Synapsin-1 proteins, and male offspring was more vulnerable than female offspring. Meanwhile, we explored the alteration of hippocampal estrogen receptors (ERs) to explain the sex specific impairment of cognitive function in low- and medium-dose BPAF groups. The results showed that perinatal BPAF exposure significantly decreased the expression of ER alpha in male offspring in a dose-dependent manner, but not in female offspring. In addition, we found that perinatal BPAF exposure can disordered the balance of oxidation and antioxidation in hippocampus of male offspring. In summary, perinatal low-dose bisphenol AF exposure impairs synaptic plasticity and cognitive function of adult offspring in a sex -dependent manner. The present results provide a pierce of potential mechanism of BPAF-caused neurodevelopmental toxicity. (c) 2021 Elsevier B.V. All rights reserved.