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

摘要： 胎儿的大脑对环境化学物质的暴露和内分泌的失调具有独特的敏感性。 系统可能会增加自闭症、注意力缺陷/多动等不良神经行为结果的风险 失调症，或抑郁症。在贝林格博士和豪泽博士的指导下，这项培训和研究计划将 以布劳恩博士作为环境流行病学家的专业知识为基础，为他的职业研究做好准备 内分泌干扰物(EDCs)及其对激素系统和儿童的影响 神经发育。布劳恩博士从未在这些领域接受过正式培训，而且很少有研究人员拥有 这种独特的跨学科专业知识。在这个奖项的K99阶段，布劳恩博士将使用教程， 研讨会/会议和教学指导，以获得以下方面的额外培训：1)内分泌学概念和 环境化学品对内分泌系统的影响；2)心理测验的选择、给药、 验证和解释；以及3)儿童神经发育。此培训将应用于原版 布劳恩博士将对25名儿童进行计算机视觉空间能力测试的研究项目 豪泽博士在两位博士的指导下进行的环境与生殖健康(地球)研究 还有贝林格。这些计算机化的测试类似于莫里斯水迷宫和放射臂迷宫，它们 用于神经毒性的动物研究。使用这些新技能和预期的健康结果 环境措施(家庭)出生队列，布劳恩博士将在R00期间解决两个具体目标- 该奖项的阶段：1)确定妊娠期双酚A/邻苯二甲酸盐暴露是否与视觉空间能力有关 在300名儿童中以及性行为是否改变了这些关联以及2)确定妊娠期双酚A/邻苯二甲酸盐暴露 与330名婴儿的胎粪性类固醇浓度有关。布劳恩博士非常适合进行这项工作 研究，因为他以前受过培训，以及他的导师、顾问和 机构。这项拟议的培训和研究将使他能够研究内分泌细胞对其他激素的影响。 以及它们是否会增加儿童不良行为后果的风险。性的检查 类固醇将促进我们对EDC作用的潜在生物学机制的了解，并将使用 动物类似物的神经行为测试将改善流行病学和动物之间的比较 学习。

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.