Human exposure to bisphenol A (BPA) is mainly due to migration from plastic packaging into food and beverages. Studies reported BPA endocrine disruptions through interactions with different nuclear receptors, including the arylhydrocarbon receptor (AhR). AhR mediates xenobiotic responses and regulates expression of drug-metabolizing enzymes (DMEs), including many CYP450s. This study aimed to assess the effects of BPA maternal exposure on CYP450s expression in fetal brain. Sprague-Dawley dams were exposed to BPA concentrations of 0, 0.5, 5, and 50 mg/L in drinking water, individually, and with nicotine. Fetal brains were isolated at gestational days GD14 and GD19, and protein expression was assessed by Western blotting. Results showed a BPA-induced significant decrease in CYP1B1 expression levels at GD14 (p = 0.001), and CYP19A1 (aromatase) expression at both mid- and late-stage development (p < 0.001). In addition, nicotine individually decreased expression levels of all examined protein targets, significantly for CYP1B1 (p < 0.001), CYP19A1 (p = 0.010), AhRR (p = 0.042), and ARNT (p < 0.001), compared to control. When combined with BPA, nicotine suppressive effects were attenuated at both GD14 and GD19. In conclusion, BPA suppresses CYP1B1 and CYP19A1 expression in fetal brain, and attenuates the suppressive effects of nicotine. Observed effects may be mediated by AhR-ARNT independent mechanisms that need further examination.
Keywords: Bisphenol A (BPA); Cytochrome P450; Endocrine disrupter; Neurodevelopmental toxicity; Nicotine.
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