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

干扰内分泌的化学物质（EDCs）会对儿童的身体发育和节奏产生不利影响

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.