双酚A（BPA）是一种多器官毒性的环境内分泌干扰物。近年来BPA免疫毒性已引起关注，但相关人群研究较少，其潜在危害效应及相关机制尚不清楚。BPA可通过表观遗传修饰改变基因表达的机制研究在非免疫细胞已得到证实。据此，我们检测孕中期妇女BPA暴露水平及新生儿脐带血Th免疫应答模式和基因甲基化水平，并配对跟踪调查婴幼儿过敏性疾病发生情况。建立生命早期不同剂量BPA暴露动物模型，研究母体BPA暴露对子代T淋巴细胞发育和分化过程相关调控基因甲基化修饰的影响，检测不同发育阶段仔鼠在过敏源刺激下的Th免疫应答模式及IgE和炎症因子水平。分离健康产妇脐带血单核细胞进行体外培养，使用DNA甲基转移酶抑制剂，进一步探讨DNA甲基化在BPA免疫毒性效应中的调控机制。以阐明生命早期BPA暴露可通过甲基化修饰影响Th1/Th2和Treg/Th17平衡，进而增加儿童过敏性疾病发生风险的分子机制。

Bisphenol A (BPA) is a kind of environmental endocrine disruptors with multiple organ toxicity. Recently, there are more concerns on the immunotoxicity of BPA, however, supporting human studies are limited. The potential health effects and mechanism underlying BPA in relation to immunotoxicity remain unclear. There are some evidences that the mechanism of BPA altering gene expression was by epigenetic regulation in non-lymphoid cells. Therefore, we will determine maternal urinary concentration of BPA in middle trimester pregnancy and the model of Th immune response in newborn cord blood and levels of DNA methylation, and their infant allergic diseases by paired tracking survey. At the same time, BPA at different doses will be administrated orally in the drinking water to establish animal model of early life BPA exposed. The effect of maternal BPA exposure on gene methylation related with controlling the development and differentiation of T lymphocyte, as well as the model of Th immune response, IgE and inflammatory factor under allergen stimulation in different development period of offspring will be analyzed. While, we will separate and culture monocyte of cord blood from healthy delivery woman to study further the regulatory mechanism of DNA methylation about BPA immunotoxicity by using inhibitor of DNA methyltransferases. Results of this study may contribution to the understanding of the molecular mechanism underlying BPA exposure during early life increasing the risk of children allergic diseases by the effect of DNA methylation modification on the balance of Th1/Th2 and Treg/Th17.