| Exposure to Bisphenol A Prenatally or in Adulthood Promotes TH2 Cytokine Production Associated with Reduction of CD4+CD25+ Regulatory T Cells Huimin Yan, Masaya Takamoto, and Kazuo Sugane Department of Infection and Host Defense, Division of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto, Japan 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, 2.5, 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- (IFN-) . However, mice prenatally exposed to BPA showed increased production of not only IL-4 but also IFN-. 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. Key words: bisphenol A, cytokine, endocrine-disrupting chemicals, prenatal exposure, regulatory T-cells. Environ Health Perspect 116:514–519 (2008) . doi:10.1289/ehp.10829 available via http://dx.doi.org/ [Online 29 January 2008]
Address correspondence to M. Takamoto, Department of Infection and Host Defense, Division of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Telephone: 81-263-37-2625. Fax: 81-263-37-3092. E-mail: masaya@sch.md.shinshu-u.ac.jp This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas 14042222 from the Ministry of Education, Culture, Sports, Science and Technology. The authors declare they have no competing financial interests. Received 31 August 2007 ; accepted 25 January 2008.
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