Involvement of estrogen receptor β in the abnormal brain development in fetuses by maternal bisphenol A diglycidyl ether exposure during gestation and lactation

Abstract

Bisphenol A diglycidyl ether (BADGE) is an epoxy resin and synthesized by reacting bisphenol A (BPA) and epichlorohydrin. BADGE has been used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In the previous studies, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. We reported that maternal BADGE exposure (1.5 mg/kg/day) during gestation and lactation periods could accelerate neuronal differentiation in the fetuses and induce anxiety-like behavior in juvenile mice. In addition, a direct BADGE (1-100 pM) exposure promoted neurite outgrowth and neuronal connection in the primary cultured cortical neurons. In this study, we examined involvement of estrogen receptor β (ERβ) in the abnormal brain development induced by BADGE exposure. The histological analysis demonstrated the increase in the ERβ-positive signals in the cortex of offspring from BADGE-exposed dams at postnatal day 1. In primary cultured cortical neurons from SD rat embryos at 15-day gestation, the elongation of neurites induced by BADGE (100 pM) treatment was significantly inhibited by ERβ antagonist ICI182,780 and GPER antagonist G15. These data suggest that BADGE exposure can accelerate neuronal differentiation via ERβ-mediated signal pathways.