The developmental origins hypothesis relates early exposures to endocrine disrupting chemicals (EDCs) to the development of chronic diseases, including metabolic syndrome, a condition affecting up to 25% of US adults and 30% of obese adolescents. Limited research in humans has considered the mechanisms by which exposures to EDCs mixtures interact with diet to alter maternal and child metabolic homeostasis, nor considered whether subsequent exposures during adolescence exacerbate risk of metabolic syndrome. Pilot human and animal data from our Formative CEHC: 'Perinatal exposures, epigenetics, child obesity and sexual maturation" (P20 ESDI 8171/ RD834800, Pl: Peterson) suggest that the disruptive effects of representative maternal EDCs on metabolic and epigenetic markers may differ across sensitive periods of child development. Drawing on unparalleled institutional resources including the UM NIEHS Center of Excellence Epigenetics Laboratory (P30 ES017885) and the Michigan Nutrition and Obesity Research Center (MNORC, P30 DK089503), this project will test the hypothesis that EDC mixtures (BPA, phthalates, lead, cadmium) via epigenetic mechanisms induce oxidative stress (tyrosine oxidation products), disrupt metabolic homeostasis (free fatty acids, amino acids, Acyl-carnitine) and lead to changes in gene transcription and metabolic function. We further hypothesize that dietary macro- and micronutrient intake and dietary patterns during pregnancy and adolescence will modify the impact of EDC mixtures on these outcomes. Study participants include the Michigan Mother-Infant Pairs (MMIP) cohort (n=80) (extension of R01 ES017005, PI: Padmanabhan) and 400 children followed from pregnancy to 8-15 years of age through our 18-yr Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) collaboration with Mexico's Instituto Nacional de Salud Publica (INSP). Findings will: 1) provide proof of concept that EDC mixtures perturb metabolic homeostasis, 2) clarify the role of diet in amplifying or negating such effects, 3) illustrate the epigenetic and transcriptional changes involved and 4) inform the design of future interventions to modify metabolic consequences of EDC exposures both in utero and during the pubertal transition.

Public Health Relevance

Metabolic syndrome affects ~25% of U.S. adults and up to 30% of obese adolescents. Understanding how exposures to EDCs during pregnancy and adolescence may interact with diet to lead to metabolic dysregulation is .highly relevant to clinical and public health practice. Results of this study will inform design of interventions to reduce health effects of toxicant mixtures in children during key developmental periods.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LKB-K)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Ann Arbor
United States
Zip Code
Sanchez-Vaznaugh, E V; Bécares, L; Sallis, J F et al. (2016) Active school transport and fast food intake: Are there racial and ethnic differences? Prev Med 91:281-286
Cantoral, A; Téllez-Rojo, M M; Ettinger, A S et al. (2016) Early introduction and cumulative consumption of sugar-sweetened beverages during the pre-school period and risk of obesity at 8-14 years of age. Pediatr Obes 11:68-74
Huang, Siying; Hu, Howard; Sánchez, Brisa N et al. (2016) Childhood Blood Lead Levels and Symptoms of Attention Deficit Hyperactivity Disorder (ADHD): A Cross-Sectional Study of Mexican Children. Environ Health Perspect 124:868-74
Baek, Jonggyu; Sánchez, Brisa N; Berrocal, Veronica J et al. (2016) Distributed Lag Models: Examining Associations Between the Built Environment and Health. Epidemiology 27:116-24
Ferguson, Kelly K; Meeker, John D; Cantonwine, David E et al. (2016) Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environ Int 94:531-7
Zhang, Zhenzhen; O'Neill, Marie S; Sánchez, Brisa N (2016) Using a latent variable model with non-constant factor loadings to examine PM2.5 constituents related to secondary inorganic aerosols. Stat Modelling 16:91-113
Baek, Jonggyu; Sanchez-Vaznaugh, Emma V; Sánchez, Brisa N (2016) Hierarchical Distributed-Lag Models: Exploring Varying Geographic Scale and Magnitude in Associations Between the Built Environment and Health. Am J Epidemiol 183:583-92
Watkins, Deborah J; Peterson, Karen E; Ferguson, Kelly K et al. (2016) Relating Phthalate and BPA Exposure to Metabolism in Peripubescence: The Role of Exposure Timing, Sex, and Puberty. J Clin Endocrinol Metab 101:79-88
Lewis, Ryan C; Johns, Lauren E; Meeker, John D (2016) Exploratory analysis of the potential relationship between urinary molybdenum and bone mineral density among adult men and women from NHANES 2007-2010. Chemosphere 164:677-682
Kasper, Nicole; Peterson, Karen E; Zhang, Zhenzhen et al. (2016) Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women. Matern Child Health J 20:1713-9

Showing the most recent 10 out of 45 publications