Prenatal exposure to Bisphenol A sex-specifically disrupts prepulse inhibition and decreases parvalbumin-positive neurons in the prefrontal cortex of adult rats

Abstract

Early-life exposure to bisphenol A (BPA) has adverse effects on neuronal development and behavioral performance; however, many aspects of its effects remain unknown. Here, we aimed to investigate whether prenatal exposure to BPA can induce psychotic-like behaviors and impair certain schizophrenia-related GABAergic markers, including GAD67, NRG1, ERbB4, and parvalbumin (PV), in the prefrontal cortex (PFC) of adult offspring rats. Pregnant Sprague-Dawley rats were orally administered BPA (0.25 and 2.5 mg/kg/day), ethinyl estradiol as a reference estrogen, or a vehicle during the pregnancy period. On postnatal days (PNDs) 62–63, male and female offspring were tested for prepulse inhibition (PPI) and locomotor activity, followed by tissue collection on PND 64. Both doses of BPA significantly decreased PPI in female offspring compared to the control group, while no significant changes were observed in male offspring. Moreover, in female offspring, a marked reduction in the density of PV-positive neurons in the PFC was observed in both BPA groups compared to the control group. In the locomotor activity test, neither sex showed significant changes. Meanwhile, the PFC expression of GAD67, NRG1, and ERbB4 genes did not show significant alterations in either male or female rats. Overall, this study demonstrates that prenatal BPA exposure disrupts PPI and decreases PV-positive neurons in the PFC of adult female rats. In other words, early neurodevelopment can be sex-specifically impaired by BPA, which may consequently increase susceptibility to schizophrenia in adulthood. Therefore, the detrimental effects of BPA on embryonic and fetal brain development should be considered in health policies related to pregnancy.