In the last 30 years, the prevalence of obesity has risen sharply among children, and minority populations are particularly vulnerable. In the CHAMACOS birth cohort, a Mexican-American population from the agricultural Salinas Valley, CA, children have a particularly high prevalence of obesity (>39% at age 9) compared to both Mexican-American children (25%) and children of all races (20%) in the United States. Changes in diet and physical activity patterns do not completely explain the current obesity epidemic. Recent research suggests that exposure to environmental obesogens, particularly during the prenatal period, may also contribute to increases in obesity. Evidence from animals and epidemiologic studies suggests that phthalates, components of plastics and cosmetics ubiquitously found in humans, may be obesogenic. For instance, as shown in animals, they can change levels of biomarkers of obesity such as adipokines, protein hormones that regulate adipogenesis. There is also growing evidence that environmental exposures can influence DNA methylation (one of the main types of epigenetic markers) and result in adverse health outcomes. However, to date, no data are available on the effects of prenatal phthalate exposure on the molecular mechanisms of obesity in children or the potential role of epigenetic dysregulation. The overall goal of this proposal is to determine whether prenatal phthalate exposure contributes to the development of childhood obesity and metabolic syndrome (MetS) and to examine whether epigenetic changes mediate this relationship. We hypothesize that in utero phthalate exposure alters DNA methylation and leads to changes in adipokines (adiponectin and leptin), oxidative stress (isoprostanes), and higher risk of obesity and metabolic MetS in children. First, we will assess whether early and/or late pregnancy exposures are associated with a) biomarkers (adiponectin, leptin and isoprostane) and b) parameters of obesity and MetS in children at 5, 9 and 14 years of age. Second, we will characterize DNA methylation patterns in children at birth and 9 years of age, and examine whether site-specific changes in the methylome (by 450K array) are associated with a) prenatal phthalate exposure and b) biomarkers and parameters of obesity and MetS. Finally, we will validate 450K array data using next generation bisulfite sequencing and the most advanced expression and bioinformatic methodologies. The proposed research utilizes the rich collection of biological samples and data on exposures, diet, activities, and health outcomes in CHAMACOS participants. By extending assessment of children to age 14, this study will include critical periods of obesity development spanning pregnancy through adolescence. Our results will help elucidate the longitudinal effects of phthalates on obesity, explore the role of epigenetics and adipokines in the development of obesity and MetS, and address important gaps in our understanding of obesity. They will also inform policies aimed at improving children's health and preventing child obesity.
Mexican-American children of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) project have a particularly high prevalence of obesity, providing a unique opportunity to study the etiology of obesity and metabolic syndrome (MetS) in a minority birth cohort. The proposed interdisciplinary study will make use of the extensive collection of biological samples and data gathered on children from early gestation through puberty. Specifically, we will examine the potential role of prenatal phthalate exposure on: obesity and MetS development;biomarkers of obesity (adiponectin and leptin), oxidative stress (isoprostanes);and epigenetic changes characterized by DNA methylation.
|Volberg, Vitaly; Yousefi, Paul; Huen, Karen et al. (2017) CpG Methylation across the adipogenic PPAR? gene and its relationship with birthweight and child BMI at 9 years. BMC Med Genet 18:7|
|Tran, V; Tindula, G; Huen, K et al. (2017) Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity. J Dev Orig Health Dis 8:196-205|
|Breton, Carrie V; Marsit, Carmen J; Faustman, Elaine et al. (2017) Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environ Health Perspect 125:511-526|
|Holland, Nina (2017) Future of environmental research in the age of epigenomics and exposomics. Rev Environ Health 32:45-54|
|Harley, Kim G; Berger, Kimberly; Rauch, Stephen et al. (2017) Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatr Res 82:405-415|
|Solomon, Olivia; Yousefi, Paul; Huen, Karen et al. (2017) Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood. Environ Mol Mutagen 58:398-410|
|Huen, Karen; Calafat, Antonia M; Bradman, Asa et al. (2016) Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children. Environ Res 148:55-62|
|Huen, Karen; Harley, Kim; Kogut, Katherine et al. (2016) DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. Pediatr Res 79:855-62|
|Holland, Nina; Huen, Karen; Tran, Vy et al. (2016) Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy. Toxics 4:|
|Erkin-Cakmak, Ayca; Harley, Kim G; Chevrier, Jonathan et al. (2015) In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS study. Environ Health Perspect 123:636-42|
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