Endocrine disruption by perfluoroalkyl substances and mercury

7.项目摘要/摘要 食用鱼类是普通民众暴露于环境污染物的主要来源， 包括持久性有机污染物，如多氯联苯、对-对-二苯基二氯乙烯 (DDE)、多溴二苯醚(PBDEs)和全氟烷基物质(PFAS)以及下列金属 即甲基汞(MeHg)。暴露在这些污染物中可能会导致内分泌功能失调， 影响类固醇和甲状腺激素以及葡萄糖和脂肪代谢。到目前为止，很少有研究表明 评估了鱼类中发现的多种污染物对内分泌功能的影响，甚至更少 认为污染物对鱼类的有害影响可以被有益的营养物质抵消 比如硒和碘。五大湖鱼类消费者研究(GLFCS)是一项持续的纵向研究 经常食用和不经常食用的食用鱼的数量。在这群人中，我们之前已经证明 多氯联苯、多溴二苯醚、滴滴涕和/或鱼类消费与各种内分泌终点的关系，包括 糖尿病发病率增加，血红蛋白A1c，甲状腺激素，甲状腺自身抗体， 类固醇激素和激素结合蛋白。我们建议利用这一独特的、具有良好特征的 队列，以测量额外的污染物暴露和营养物质，即全氟辛烷磺酸、汞和硒 储存了490名研究参与者的生物样本。具体来说，我们将(1)确定关键措施是否 GLFCS队列中的内分泌功能与接触全氟辛烷磺酸和汞有关 与多氯联苯、DDE和多溴二苯醚混合暴露；以及(2)调查血清硒和尿硒水平 碘对内分泌功能的影响与全氟辛烷磺酸、汞、多氯联苯、DDE和PBDEs的关系。我们还将 探讨汞和全氟辛烷磺酸与自报事件和流行内分泌疾病的关系 包括糖尿病、甲状腺功能减退症和高脂血症。目前可获得的暴露和营养 测量包括血清多氯联苯、DDE和多溴二苯醚、尿碘和估计的汞摄入量 报告的鱼类消费量。目前可用的结果测量包括自我报告的糖尿病， 糖尿病前期、甲状腺功能减退；甲状腺激素、性类固醇激素、促性腺激素、激素结合 蛋白质、自身抗体和糖脂动态平衡的标志物。我们将使用这两种标准(线性、 Logistic和Cox比例风险回归模型)和替代性(弹性净值；倾向分数 调整.加权分位数和回归)评估个体关联性的分析方法 带有内分泌失调标志的化学品和污染物混合物。这项调查是 有望使人们更好地了解污染物对内分泌功能和疾病的影响 这将指导消费者关于食用鱼类的风险和益处的建议。

7. Project Summary/Abstract Consumption of fish is a major source of exposure to environmental contaminants for the general population, including persistent organic pollutants such as polychlorinated biphenyls (PCBs), p,p’-diphenyldichloroethene (DDE), polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFAS), as well as metals such as methyl mercury (meHg). Exposure to these pollutants may cause dysregulation of endocrine function, affecting steroid and thyroid hormones as well as glucose and lipid metabolism. To date, few studies have evaluated the impact of multiple contaminants found in fish on endocrine function, and even fewer have considered that the harmful effects of contaminants in fish may be counterbalanced by beneficial nutrients such as selenium and iodide. The Great Lakes Fish Consumer Study (GLFCS) is an ongoing longitudinal study of both frequent and infrequent consumers of sport fish. In this population, we have previously demonstrated associations of PCBs, PBDEs, DDE and/or fish consumption with various endocrine endpoints, including increased diabetes incidence and changes in hemoglobin A1c, thyroid hormones, thyroid autoantibodies, steroid hormones and hormone binding proteins. We propose to leverage this unique, well characterized cohort to measure additional contaminant exposures and nutrients, namely PFAS, Hg, and selenium, in banked biosamples from 490 study participants. Specifically, we will (1) determine if key measures of endocrine function in the GLFCS cohort are associated with exposure to PFAS and mercury individually and in mixed exposures with PCBs, DDE and PBDEs; and (2) investigate if levels of serum selenium and urinary iodide impact associations of endocrine function with PFAS, mercury, PCBs, DDE and PBDEs. We will also explore associations of mercury and PFAS on self-reported incident and prevalent endocrine disease, including diabetes, hypothyroidism and hyperlipidemia.Currently available exposure and nutrient measurements include serum PCBs, DDE, and PBDEs, urinary iodide, and estimated mercury intake from reported fish consumption. Currently available outcome measurements include self-reported diabetes, prediabetes, hypothyroidism; thyroid hormones, sex steroid hormones, gonadotropins, hormone binding proteins, autoantibodies and markers of glucose and lipid homeostasis. We will use both standard (linear, logistic and Cox proportional hazards regression models) and alternative (elastic net; propensity score adjustment; weighted quantile sum regression) analytic approaches to evaluate associations of individual chemicals and mixtures of contaminants with markers of endocrine dysregulation. This investigation is expected to lead to a better understanding of the effects of pollutants on endocrine function and disease in adults, which will guide advice to consumers on the risks and benefits of fish consumption.