Endocrine Disruptors: Maternal Estrogen, Metabolism and Fetal Fatty Acid Supply

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 DESCRIPTION (provided by applicant): This K99/R00 will prepare Dr. Rita Strakovsky for an independent research career. Dr. Strakovsky has extensive training using animal models to address questions related to maternal health, but has a strong desire to expand her training to epidemiology. An exceptional team of mentors has been assembled with expertise in epidemiology, biostatistics, environmental health, and reproductive/endocrine toxicology. Two mentors have extensive experience integrating animal and human research. The primary training goal is to develop expertise in environmental epidemiology, with the eventual goal of applying knowledge from mechanistic lab animal research when formulating epidemiologic research questions. The career development plan includes rigorous course work in epidemiology/biostatistics as well as mentored research in environmental epidemiology. Women of reproductive age are exposed to bisphenol A (BPA) and phthalates on a daily basis. These chemicals can disrupt estrogen synthesis in animal models, but no human studies have assessed the relationship between BPA or phthalates and estrogen during pregnancy. Furthermore, no studies have assessed whether maternal adiposity can modify this relationship. In the mentored phase, Dr. Strakovsky will leverage an ongoing pregnancy cohort to investigate the association between these chemicals and maternal estrogen levels, and whether maternal % body fat or waist/hip ratio can modify this relationship (Aim 1). BPA and phthalates will be assessed in pooled urine from 5 samples collected across pregnancy. Estrogens will be measured in 3 urine samples collected at the low, middle, and peak concentrations of gestational estrogen. It is hypothesized that women with higher urinary BPA or phthalate metabolites across pregnancy will have lower urinary estrogen metabolites throughout pregnancy, and maternal % body fat and waist/hip ratio and/or the infant's sex will modify this relationship. Factors that affect estrogen levels in the mother could alter the accretion and release of maternal adipose tissue stores, and thus fetal LC-PUFA supply, which is critical for neurodevelopment. Studies in rodents show that BPA and phthalates can alter placental LC-PUFA content (which is directly related to fetal LC-PUFA supply), but it is not known whether this also occurs in humans. In the independent phase, Dr. Strakovsky will investigate the relationship between maternal BPA and phthalate exposures and fetal LC-PUFA supply (Aim 2). Cord blood collected at birth will be used to measure arachidonic, linoleic, α-linolenic, docosahexaenoic, and the n-6/n-3 fatty acid ratio. It is hypothesized that higher urinary BPA or phthalate metabolites across pregnancy will be associated with increased n-6/n-3 ratio, and decreased cord blood LC-PUFAs. It is further hypothesized that the association of BPA or phthalates with maternal estrogen will mediate this relationship, and that the relationship will be modified by the infant's sex. These findings will provide novel information regarding the impact of two widespread environmental toxicants on maternal and fetal health.