围产期双酚S暴露致胰岛β细胞损伤的IGF2/H19表观遗传学机制研究

双酚S（Bisphenol S, BPS）因较强的热稳定性而被认为是一种“安全”的双酚A（Bisphenol A, BPA）替代品，已取代BPA应用于婴儿奶瓶等塑料制品中，但其在人群样本中仍广泛检出，因此引发大量关注。项目组前期发现围产期BPA暴露能诱发胰岛β细胞受损和机体糖耐量异常。鉴于BPS有与BPA极相似的结构和雌激素效应，且我们初步的β细胞实验发现BPS暴露减少胰岛素分泌，提示BPS的损伤效应可能存在。为深入探讨BPS在围产期暴露对胰岛β细胞的影响，本项目拟通过建立小鼠围产期BPS暴露模型，研究对子代机体血糖稳态和胰岛β细胞结构、功能的影响，结合对印记基因IGF2/H19 DNA甲基化和组蛋白修饰等表观遗传学的深入研究，探索BPS对胰岛β细胞影响的可能机制。本项目成果将明确围产期BPS暴露影响血糖稳态的内在表观遗传学机制，为新型环境内分泌干扰物的健康风险评价及合理预防提供科学依据。

Due to the strong thermal stability, Bisphenol S (BPS) once considered as a safe substitute of Bisphenol A (BPA) and has been widely applied in the plastic products including baby bottles. However, it’s still widely detectable in human samples, which has drawn much attention. Previously, we found that prenatal BPA exposure could induce significant impairment of pancreatic β-cells and glucose intolerance. As BPS has quite similar structure and estrogen effect with BPA, and our preliminary experiments showed that BPS exposure could reduce the insulin secretion, which suggests the adverse effect of BPS on pancreatic β-cells. To further study the effect of BPS exposure on the pancreatic β-cells during prenatal period, we propose to study the glucose homeostasis, pancreatic β-cell structure and functions in the offspring of a mouse model that prenatally exposed to BPS. For the potential epigenetic regulations, i.e. DNA methylation and histone modification, we plan to explore the possible mechanisms of BPS-induced dysfunction of pancreatic β-cells. The findings of the project could uncover the potential epigenetic mechanisms of prenatal BPS exposure on the glucose homeostasis, and provide scientific basis for the health risk assessment and rational prevention of new environmental endocrine disruptors.