Neurobehavioral effects of Bisphenol A Across age and sex

描述（由申请人提供）：人类暴露于聚碳酸酯塑料，环氧树脂和无碳热收据等产品中的双酚A （BPA）几乎无处不在。大量对物种的研究表明，在发育的关键窗口期暴露于双酚a会改变社会性、情绪、学习和记忆相关的行为，这引起了人们的关注，特别是在妊娠期和生命早期暴露于双酚a可能会导致儿童和成人行为障碍的发生率增加。因为到目前为止，大多数研究都不是专门设计来指导人类风险评估的，利用国家毒理学计划/食品和药物管理局（NTP/FDA）对Sprague Dawley大鼠的慢性暴露研究来表征围产期BPA暴露如何影响焦虑，记忆相关，通过三种与人类相关的剂量，研究青少年和成年时期的交配和配偶偏好行为，将获得关键数据，可以为有关BPA潜在健康影响的公共政策提供信息。这些拟议的研究将检验BPA通过改变海马体和下丘脑的性别特异性发育程序来破坏行为反应的假设，可能通过改变表观遗传景观和随后的基因表达。目的1的工作将确定妊娠暴露对新生大鼠下丘脑和海马遗传和表观遗传表达的影响。目标2的研究将评估BPA对男女青少年焦虑、活动和记忆相关行为的影响，目标3的研究将描述慢性BPA暴露如何影响成人的社会性行为和认知行为，并确定新生儿生活中海马和下丘脑DNA甲基化和基因表达变化是否永久性的，是否与观察到的行为变化相关。这些研究将提供关键的观察和机制见解，以了解早期暴露于双酚a是否会增加儿童性别特异性行为异常的风险。

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.