Obesity and related cardio-metabolic health disorders are leading causes of morbidity and mortality among women. The rapidly increasing worldwide prevalence of these disorders suggests that risk factors other than genetics, diet, and physical activity are involved. Environmental factors, such as endocrine disrupting chemicals (EDC), likely play an important role in modifying the response to dietary nutrients. Bisphenol A (BPA) and phthalates are examples of EDCs that are ubiquitous in our environment and may contribute to the development of metabolic disorders by interfering with glucose and lipid metabolism and energy balance. Much of the current research focuses on exposures during stages of early life growth and development. However, pregnancy is a relatively unappreciated sensitive life stage in adults that is associated with numerous physiologic changes, which may have lasting consequences for women's health. Associations of exposures to BPA and phthalates during pregnancy and the development of cardio-metabolic health indicators in women during the long-term postpartum period have not yet been investigated. The candidate has a strong foundation in the methodological and analytical skills related to nutritional and reproductive epidemiology. The intent of this application is in seeking a Pathway to Independence Award to gain the additional training needed to accomplish the following long-term career goal: to establish an independent research program to investigate the intersection of environmental and nutritional factors related to disease development, progression, and treatment. The training component of this project will be based in the Department of Preventive Medicine (DPM) at Mount Sinai School of Medicine. The DPM is internationally renowned for excellence in innovative, interdisciplinary research in public health, epidemiology, environmental health, and social sciences. The mentors, Drs. Susan Teitelbaum and Robert Wright, are experts in the field of environmental health and the advisory team, Drs. Mary Wolff, Andrea Baccarelli, Brent Coull, and Mara Tellez-Rojo, possesses complementary areas of expertise to address training and research goals. The proposed training plan includes formal coursework, directed readings, attendance to scholarly seminars and meetings, and mentored career development activities, as well as rotations in Dr. Wright's molecular biology and analytical chemistry laboratories. From this training, the idea is to gain knowledge and skills related to environmental health and EDCs, toxicology, epigenetics, and advanced statistical analysis, which will be applied during the research component of this project. The proposed research will determine whether exposures to BPA and phthalates during pregnancy and the postpartum are associated with the development of adiposity and cardio-metabolic health indicators in women. This research will be conducted by leveraging data regarding maternal exposures and health outcomes collected from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) study (R01 ES013744 and R01 ES021357 BPA, Phthalates &Stress: Mechanisms and Interactions for Childhood Obesity), a prospective birth cohort in Mexico. The following aims will be accomplished: 1) Determine whether exposures to BPA and phthalates in pregnancy and the postpartum are associated with the development of adiposity and cardio-metabolic health indicators in adult women up to 7 years postpartum. 2) Determine whether exposure to BPA and phthalates modifies the association of dietary fat with the development of adiposity and cardio-metabolic health indicators. 3) Determine the role of DNA methylation as a mediator of the associations of BPA and phthalates and the development of adiposity and cardio-metabolic health indicators. DNA methylation of nuclear receptor genes that are involved in body weight homeostasis will be measured: glucocorticoid receptor, ER?, and PPAR?. The training and research activities will result in scientific presentations and publications, and will prepare me to successfully compete for R01 funding during the R00 phase.
BPA and phthalates are EDCs that are ubiquitous in our environment and may contribute to the development of metabolic disorders by interfering with glucose and lipid metabolism and energy balance. Pregnancy represents a life stage with numerous physiological changes, which stress the metabolic system and have lasting consequences for women's health, including diabetes and cardiovascular disease risk factors. This study will determine whether exposures to BPA and phthalates in pregnancy and the postpartum are associated with the development of adiposity and cardio-metabolic health indicators measured in adult women up to 7 years postpartum.