Epigenetic Effects of Prenatal Arsenic Exposure and Fetal Growth

Molly Kile, MS, ScD is an environmental epidemiologist and a Research Associate at Harvard School of Public Health. This application is for a K01 Mentored Career Development Award combines formal education, structured mentorship and training with a detailed research plan that will allow Dr. Kile to become an independent investigator who specializes in perinatal environmental epidemiology capable of investigating epigenetic-environmental interactions associated with prenatal exposure to environmental chemicals. Epidemiological and experimental studies suggest that the intrauterine environment may represent a biologically sensitive window for chemicals that may impair growth and organ development that result in adverse health outcomes later in life. While the mechanisms behind these relationships are unclear, it has been hypothesized that epigenetic dysregulation is involved. Prospective longitudinal birth cohorts in exposed populations are the optimal design to study the effects of in utero chemical exposures and epigenetic- environmental interactions that could lead to life-long phenotypic changes. For this award, Dr. Kile will use data collected from 3 prospective longitudinal birth cohorts that were specifically designed to evaluate the effects of prenatal metal exposure on perinatal and pediatric health outcomes to 1) examine the association between prenatal arsenic exposure, a common environmental pollutant, and fetal growth; 2) investigate the interaction between arsenic and DNA methylation of endothelial nitric oxide gene (eNOS) and the insulin-like growth factor gene (Igf2) which are well characterized and involved in fetal growth and development using umbilical cord leukocytes and umbilical vein endothelials cells; and 3) explore the association between Igf2 gene DNA methylation and fetal growth. Dr. Kile is well positioned to carry out the proposed studies because of her prior research experience in molecular environmental epidemiology and the unique resources available through her mentorship team including access to 3 large established prospective longitudinal birth cohorts that will provide the necessary exposure assessment data, genetic material, newborn measurements and covariate data during this award period; access to state-of-the-art molecular biological laboratories; and, advanced coursework in perinatal epidemiology and epigenetics. The proposed human studies will fill important research gaps in our knowledge of arsenic toxicity and its potential to impact human development that can inform clinical and public health interventions. The proposed training and career development will enable Dr. Kile make substantial scientific contributions and develop the knowledge and skills necessary to become an independent investigator and position her to become a leader in the field of perinatal environmental epidemiology. Public Health Relevance: Adverse fetal growth can lead to low birthweight which is associated with increased morbidity and mortality. As such, understanding the factors that contribute to adverse fetal growth is a public health priority. The proposed studies will fill important research gaps in our knowledge of arsenic toxicity and its impact on fetal growth that could inform both clinical and public health interventions in developing and developed countries.