Abstract:Objective:To investigate the expression of amyloid precursor protein (APP),microtubule-associated protein (Tau),and phosphorylated Tau protein (p-Tau) of offspring mouse hippocampus after perinatal exposure of F0 mice to bisphenol A (BPA) on different stages,and identify critical windows for fetal development stage susceptibility to BPA exposure in male and female mice. Methods:Theprimary cultured hippocampus neurons of C57BL/6J fetal mice receiued with BPA;F0 mice received perinatal subcutaneous injection of BPA to establish the mouse BPA exposure model. Four groups were classified by different exposure stages,including the control,the fetus period (P6-PND0),the lactating period (PND0-PND21) and the combined exposure (P6-PND21) groups. The expressions of APP,p-Tau and Tau in offspring mouse(8-month-old) hippocampus were detected by Western blotting assays. Results:The expressions of APP,p-Tau and Tau protein of hippocampal neurons were increased in a dose dependent manner after incubation with varied concentrations of BPA. BPA obviously increased APP,p-Tau and Tau expressions in the PND0-PND21 and the P6-PND21 group of female mice;for the male mice,the three proteins' up-regulation was observed only in the P6-PND21 group. Conclusion:Continuous perinatal exposure to BPA could contribute to the up-regulation of APP,p-Tau and Tau,which might subsequently result in neuronal injury. Moreover,female mice are more susceptible to BPA exposure than male mice.