Exposure to bisphenol A prenatally or in adulthood promotes TH2 cytokine production associated with reduction of CD4+CD25+ regulatory T cells

Abstract

Background: Bisphenol A (BPA) is a widespread endocrine-disrupting chemical that can affect humans and animals. Objectives: We investigated the effects of adult or prenatal exposure to BPA on T-helper (TH)1/TH2 immune responses and the mechanisms underlying these effects. Methods: To evaluate the effects of exposure to BPA in adulthood, male Leishmania major-susceptible BALB/c and -resistant C57BL/6 mice were subcutaneously injected with 0.625, 1.25, 2.6, and 5 μmol BPA 1 week before being infected with L. major. To evaluate prenatal exposure, female mice were given BPA-containing drinking water at concentrations of 1, 10, and 100 nM for 2 weeks, then mated, and given BPA for another week. Male 10-week-old offspring were infected with L. major. Footpad swelling was assessed as a measure of the course of infection. Results: Mice exposed to BPA prenatally or in adulthood showed a dose-dependent increase in footpad swelling after being infected with L. major. Exposure to BPA in adulthood significantly promoted antigen-stimulated production of interleukin (IL)-4, IL-10, and IL-13 but not interferon-γ (IFN-γ). However, mice prenatally exposed to BPA showed increased production of not only IL-4 but also IFN-γ. The percentages of CD4+CD25+ cells were decreased in mice exposed to BPA either prenatally or in adulthood. Effects of prenatal BPA exposure were far more pronounced than effects of exposure in adulthood. Conclusion: BPA promotes the development of TH2 cells in adulthood and both TH1 and TH2 cells in prenatal stages by reducing the number of regulatory T cells.