US EPA

3973695 

Technical Report 

Epigenetic Changes After Intrauterine Exposure to Endocrine Disrupting Chemicals 

Michels, K 

2009 

NIH_RePORTER2009/K01ES015771-03 

English 

DESCRIPTION (provided by applicant) The candidate is an epidemiologist and biostatistician with 10 years experience in conducting population-based observational studies. The application describes a 3-year career development plan that will provide the candidate with the formal training and laboratory research experience necessary for her development as an independent investigator in epigenetic epidemiology of chemical exposures in utero and chronic diseases. The candidate's long-term career objective is to develop an academic program of research that combines epidemiologic, molecular, and epigenetic principles to study the complex associations of genes, their expression, and environmental factors in the etiology of cancer. The training component includes mentorship by an environmental cancer biologist and six-month rotations annually in an environmental genetics and epigenetics laboratory in additional to formal course work education. The research component describes a prospective investigation of endocrine-disrupting chemical (EDC) levels in maternal urine collected during pregnancy and relation to methylation and imprinting status of growth factors and methylation status of the ERa gene in cord blood from offspring. It is hypothesized that intrauterine exposure to synthetic EDCs including, bisphenol A and the phthalates di-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBF), and butyl benzyl phthalate (BBP), present at significant levels in the environment, induces loss of imprinting of insulin-like growth factor 2 and hypomethylation of the imprinting control region of the LIT1 gene on chromosome 11p15. Further it is hypothesized that intrauterine exposure to bisphenol A and the phthalates DEHP, DBP, and BBP induces hypomethylation of the ERa gene and thereby increases ERa transcription expression. Urine samples of pregnant women will be collected and EDC levels will be measured at the Centers for Disease Control. Cord blood samples will be collected at delivery and DNA methylation and imprinting status will be determined. Features of this design include state-of-the art exposure ascertainment, sufficient statistical power to detect exposure-related variation in epigenetic control of gene expression, and efficient control for potential confounding variables.