Epigenetic and Developmental Effects of In Utero Exposure to Environmental Toxicants

Metabolic diseases such as obesity and diabetes are modern day epidemics. Early life exposure
to an adverse developmental environment, including environmental toxins, are linked to
increased susceptibility to obesity, metabolic syndrome and type 2 diabetes. Although the
mechanisms underlying the fetal origins of metabolic disease are poorly understood, strong
evidence suggests that alterations in the epigenome play a critical role in this process. The
central hypothesis of this proposal is that intrauterine exposure to benzo[a]pyrene leads to
epigenetic changes which will have functional consequences and may be a marker for, or may
contribute to, increased susceptibility to adverse outcomes in childhood including increased
adiposity and the subsequent development of obesity, metabolic syndrome or diabetes. The
goals of this proposal are to: 1) determine benzo[a]pyrene levels in umbilical cord blood of
newborns, 2) determine whether benzo[a]pyrene exposure during pregnancy correlates with early
onset of obesity and metabolic disease by examining the children at 12 and 24 months of age,
3) determine whether in utero benzo[a]pyrene exposure programs metabolic disease through
alterations in DNA methylation and gene expression, and 4) determine the plasticity of the
DNA methylation patterns in the same offspring at 12 months of age. The long-term goal of
this project is to define biomarkers that identify neonates at "high-risk" for diminished
attainment of full health potential, who can then be targeted for preventative measures.