High-Dimensional Epigenomic and Metabolomic Responses to Metal and EDC Exposures

内分泌干扰物(EDCs)会对儿童的身体发育和节奏产生不利影响 并与成人慢性疾病的发展有关，例如肥胖症、2型 糖尿病和心血管疾病。代谢综合征，这些结果的一系列， 影响多达25%的美国成年人和30%的肥胖青少年。关于发育起源的研究已经 主要关注早期生活暴露，较少关注EDC混合物在 青春期过渡可能会加剧代谢后果，导致代谢综合征。 关于母亲产前饮食对慢性疾病发育起源的影响的研究尚未得到 与环境健康研究很好地结合在一起，尽管越来越多的证据表明营养是 通过对吸收、分布和/或毒性的影响而对环境污染物的敏感性。 饮食调节的假说机制包括下调参与的信号通路 炎症反应，对氧化应激的保护，以及代谢稳态的恢复。 因为营养素可以作为环境化学品毒性效应的激动剂或拮抗剂。 根据剂量等因素，需要更多的研究来准确确定它在 改变环境毒物的影响和疾病的未来发展。此应用程序的目标是 了解接触EDC混合物(双酚A、邻苯二甲酸盐、铅、镉)的机制 在子宫和青春期期间与饮食相互作用，影响代谢稳态、氧化应激和 代谢综合征的风险..利用两个现有的人类队列[墨西哥早期生活暴露于 环境毒物(元素)和密歇根母婴配对(MMIP)]和活的黄色 Aggi小鼠模型，这个中心的重点是解剖EDC混合物的影响及其相互作用 饮食对新陈代谢健康的影响。研究结果将揭示表观遗传和转录变化 导致生长、成熟和代谢结果的变化，并为 设计未来干预措施，以减少无处不在的儿童疾病对儿童健康的影响。 相关性(见说明)； 在儿童发育的不同时期暴露于内分泌干扰物(EDCs)可能 影响生长、成熟速度和代谢综合征的风险，但这些影响可能被放大或 因饮食摄入而受潮。通过该中心进行的研究将有助于更好地了解 化学物质和饮食如何相互作用，并为未来改善儿童健康的干预措施的设计提供信息。

Endocrine-disrupting chemicals (EDCs) can have adverse impacts on children's physical growth and tempo of maturation and have been related to development of adult chronic conditions, e.g., obesity, type 2 diabetes mellitus and cardiovascular disease. Metabolic syndrome, a constellation of these outcomes, affects up to 25% of US adults and 30% of obese adolescents. Research on developmental origins has focused primarily on early life exposures, with less attention on the role exposures to EDC mixtures during the pubertal transition may play in exacerbating metabolic consequences leading to metabolic syndrome. Research on the effects of maternal prenatal diet on developmental origins of chronic disease has not been well integrated with environmental health research, despite growing evidence that nutrition is a modulator of susceptibility to environmental pollutants through effects on absorption, distribution, and/or toxicity. Hypothesized mechanisms for dietary modulation include down-regulation of signaling pathways involved in the inflammatory response, protection against oxidative stress, and restoration of metabolic homeostasis. Because nutrients may serve as agonists or antagonists of toxic effects of environmental chemicals depending on factors such as dose, more studies are necessary to accurately determine the role it plays in altering the effects of environmental toxicants and the future development of disease. This application aims to understand the mechanisms by which exposure to EDC mixtures (BPA, phthalates, lead, cadmium) interact with diet in utero and peripuberty to impact markers of metabolic homeostasis, oxidative stress and risk of metabolic syndrome.. Capitalizing on two existing human cohorts [Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) and the Michigan Mother-Infant Pairs (MMIP)] and the viable yellow agouti mouse model, the focus of this center is to dissect out the impact of EDC mixtures and its interaction with diet on metabolic health. Research findings will shed light on epigenetic and transcriptional changes leading to changes in growth, maturation and metabolic outcomes, and provide an invaluable base for designing future interventions to reduce the impact of pervasive EDCs on children's health. RELEVANCE (See instructions); Exposure to endocrine disrupting chemicals (EDCs) during different periods of child development can impact growth, tempo of maturation and risk of metabolic syndrome, but these effects may be amplified or dampened by dietary intake. Research conducted through this center will foster a better understanding of how chemical and diet interact and inform the design of future interventions to improve children's health.