Neurobehavioral effects of Bisphenol A Across age and sex

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DESCRIPTION (provided by applicant): Human exposure to Bisphenol A (BPA), found in polycarbonate plastics, epoxy resins, and carbonless thermal receipts, among other products, is nearly ubiquitous. Numerous studies in a range of species have shown that BPA exposure during critical windows of development alters sociosexual, mood, learning and memory-related behaviors raising concern that BPA exposure, particularly during gestation and early life, might be contributing to increased incidences of behavioral disorders in children and adults. Because most studies to date were not specifically designed to guide human risk assessment, leveraging the National Toxicology Program/Food and Drug Administration (NTP/FDA) chronic exposure study in Sprague Dawley rats to characterize how perinatal BPA exposure affects anxiety, memory-related, copulatory and mate preference behaviors during juvenile and adult life across three human-relevant doses will yield critical data that can inform public policy regarding the potential health effects of BPA. These proposed studies will test the hypothesis that BPA disrupts behavioral responses by altering sex specific developmental programming of the hippocampus and hypothalamus, potentially by altering the epigenetic landscape and subsequent gene expression. Work in aim 1 will establish the impact of gestational exposure on genetic and epigenetic expression in the hypothalamus and hippocampus of newborn rats. Studies in aim 2 will evaluate the effects of BPA on anxiety, Activity and memory-related behaviors in juveniles of both sexes and work in aim 3 will characterize how chronic BPA exposure affects sociosexual and cognitive behavior in adults, and determine if hippocampal and hypothalamic DNA methylation and gene expression changes seen in neonatal life are permanent and correlate with observed behavioral changes. These studies will provide critical observational and mechanistic insights into whether or not early exposure to BPA increases the risk for behavioral abnormalities in a sex-specific manner in children.