Prenatal Sex Steroids, Bisphenol A, Phthalates, and Sexually Dimorphic Behaviors

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Abstract: The fetal brain is uniquely sensitive and environmental chemical exposures and dysregulation of the endocrine system may increase the risk of adverse neurobehavioral outcomes like autism, attention-deficit/hyperactivity disorder, or depression. Under the mentorship of Drs. Bellinger and Hauser, this training and research plan will build upon Dr. Braun's expertise as an environmental epidemiologist and prepare him for a career studying endocrine disrupting compounds (EDCs) and their impact on hormonal systems and childhood neurodevelopment. Dr. Braun has never received formal training in these areas and few researchers possess this unique cross-disciplinary expertise. During the K99-phase of this award Dr. Braun will use tutorials, seminars/conferences, and didactic instruction to gain additional training in: 1) endocrinology concepts and the impact of environmental chemicals on the endocrine system; 2) psychometric test selection, administration, validation, and interpretation; and 3) childhood neurodevelopment. This training will be applied in an original research project where Dr. Braun will administer computerized tests of visuospatial ability to 25 children from Dr. Hauser's Environment and Reproductive Health (EARTH) study under the guidance of both Drs. Hauser and Bellinger. These computerized tests are analogues of the Morris Water Maze and Radial Arm Maze, which are used in animal studies of neurotoxicity. Using these new skills and the prospective Health Outcomes and Measures of the Environment (HOME) birth cohort, Dr. Braun will address two specific aims during the R00- phase of this award: 1) determine if gestational BPA/phthalate exposure is associated with visuospatial ability in 300 children and if sex modifies these associations and 2) determine if gestational BPA/phthalate exposure is associated with meconium sex steroid concentrations in 330 infants. Dr. Braun is well suited to carry out this research because of his prior training and the unique resources offered by his mentors, advisors, and institution. This proposed training and research will enable him to study the impact of EDCs on other hormonal systems and whether they increase the risk of adverse childhood behavioral outcomes. The examination of sex steroids will advance our knowledge of potential biological mechanisms of EDC action and the use of neurobehavioral tests with animal analogues will improve comparisons between epidemiological and animal studies.