THE COLUMBIA CENTER FOR CHILDREN’S ENVIRONMENTAL HEALTH

Obesity Project:1) To test whether prenatal and early-life exposures to the endocrine disrupters polycyclic aromatic hydrocarbon (PAH) and bisphenol A (BPA) predict body size growth trajectories and childhood obesity at age 8-10 years. This will be accomplished by following our ongoing birth cohort to age 8-10 years, measuring height and weight at ages 5, 7, 8-10, body composition at age 7, 8-10, and metabolic syndrome components at age 8-10 years. This work takes advantage of sophisticated geographic information system based data on the children's neighborhoods to control for social (e.g., poverty and socio-demographic composition) and physical factors (e.g., playgrounds, parks, fast-food vendors) likely to predict childhood obesity.2) To determine whether differences in the methylation status of key genes involved in adipogenesis (PPARv2, C/EBPq, C/EBPli, C/EBP6 and DLK1), appetite control (FTO) mediate the association between xenobiotic exposures and childhood obesity outcomes. Methylation of these genes will be measured in cord white blood cell DNA by pyrosequencing.Neurodevelopmental Project:1) To determine whether prenatal exposures to the endocrine disrupters, PAH and BPA, are associated with adverse neurobehavioral outcomes in peri-pubertal children, as measured by diagnostic assessment of child psychopathology and cognitive functioning.2) To determine whether prenatal exposure to PAH or BPA is associated with epigenetic changes in umbilical cord white blood cells (DNA methylation validated by gene expression) in candidate genes/pathways is associated with endocrine disruption and immune dysregulation, and whether altered methylation and gene expression in these candidates is associated with the neurobehavioral outcomes.3) To determine the extent to which neighborhood-level conditions contribute to neurobehavioral outcomes and/or moderate the individual-level associations between exposure to PAH or BPA and child neurodevelopment using GIS.Mechanistic Core:1) To examine the consequence of prenatal oral BPA exposure on neurobehavioral, obesity and immune dysfunction in Balb/c mice by determining whether prenatal BPA exposure is associated with abnormal brain cytoarchitecture; impaired social, anxiety-like and cognitive performance; greater adult body weight; body fat composition; and organ fat and immune dysfunction in the adult offspring or grand offspring. 2) To examine the consequence of prenatal oral BPA exposure for tissue-specific molecular modifications in mice by determining prenatal BPA exposure-induced changes in DNA methylation in genes sensitive to endocrine disruption and immune dysregulation in the brain (hippocampus, hypothalamus, cortex), adipocytes and blood of the prenatally BPA exposed offspring and grand-offspring at gestation day 19 and adulthood (PND 60). Determine corresponding changes in gene expression, neurobehavioral, obesity and immunologic outcomes, and whether changes in DNA methylation and gene expression of genes critical for adipogenesis persist in blood of F1 male offspring from PND 28 to adulthood. 3) To examine the consequence of prenatal inhaled PAH exposure at current levels determined to exist in New York City's Northern Manhattan/South Bronx on neurodevelopment and obesity in Balb/c mice by determining whether prenatal PAH exposure is associated with abnormal brain cytoarchitecture, impaired anxiety-like and cognitive performance, greater body weight through weaning to adulthood, body fat composition, and organ fat content in adult offspring and grand offspring. 4) To examine the consequence of prenatal inhaled PAH exposure for tissue specific molecular modifications (DNA m