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

产前性类固醇、双酚 A、邻苯二甲酸盐和性别二态行为

• 批准号: 8300259
• 负责人: Joseph M Braun
• 金额: $ 8.42万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-13 至 2013-02-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8300259
• 关键词: 8 year old; 9 year old; Address; Affect; Aggressive behavior; Amniotic Fluid; Androgens; Androstenedione; Animals; Archives; Area; Attention deficit hyperactivity disorder; Attenuated; Autistic Disorder; Award; Behavior; Behavioral; Biological; Biological Markers; Birth; Boston; Brain; Chemicals; Child; Childhood; Clinical; Data; Disease; Endocrine Disruptors; Endocrine disruption; Endocrine system; Endocrinology; Environment; Epidemiologist; Epidemiology; Estradiol; Estrogens; Estrone; Exposure to; Female; Fetal Development; Fetus; Gonadal Steroid Hormones; Health; Human; Individual; Infant; Institution; Instruction; Intervention; Knowledge; Learning; Learning Disabilities; Measures; Meconium; Mediating; Medical; Memory; Mental Depression; Mentors; Mentorship; Methods; Nature; Outcome; Outcome Measure; Pathway interactions; Performance; Perinatal Exposure; Phase; Play; Population; Pregnancy; Pregnant Women; Process; Psychometrics; Public Health; Radial; Reproductive Health; Research; Research Personnel; Research Project Grants; Research Training; Resources; Risk; Rodent; Role; Sampling; Sex Characteristics; Short-Term Memory; Testing; Testosterone; Time; Toxicant exposure; Training; Umbilical Cord Blood; United States; Urine; Validation; Visuospatial; Work; analog; arm; bisphenol A; career; cohort; computerized; critical period; environmental chemical; environmental chemical exposure; experience; fetal; improved; male; morris water maze; multidisciplinary; neurobehavior; neurobehavioral; neurobehavioral disorder; neurobehavioral test; neurodevelopment; neurotoxicity; novel; performance tests; phthalates; prenatal; prospective; public health relevance; research study; sex; skills; steroid metabolism; symposium; urinary; virtual

DESCRIPTION (provided by applicant) 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. Public Health Relevance: Neurobehavioral disorders place an enormous burden on educational and medical resources; thus, priority is to understand factors associated with these disorders. The proposed studies could inform public health interventions by addressing important research gaps in our knowledge of BPA and phthalate neurotoxicity and its impact on human neurobehavior. Public Health Relevance: The fetus may be susceptible to endocrine disrupting compounds like bisphenol A (BPA) and phthalates. Exposure to these compounds may be detrimental to childhood neurodevelopment by disrupting gestational sex steroid metabolism. This application will use an integrated training plan in endocrine disruption and childhood neurodevelopment to prepare Dr. Joe M. Braun to produce high-quality research studying the impact of gestational BPA/phthalate exposures on fetal sex steroids and childhood visuospatial ability.

描述（由申请人提供） 胎儿大脑具有独特的敏感性，环境化学物质暴露和内分泌系统失调可能会增加不良神经行为结果的风险，如自闭症、注意力缺陷/多动症或抑郁症。在博士的指导下。 Bellinger 和 Hauser 表示，这项培训和研究计划将以 Braun 博士作为环境流行病学家的专业知识为基础，为他从事研究内分泌干扰化合物 (EDC) 及其对荷尔蒙系统和儿童神经发育的影响的职业生涯做好准备。布劳恩博士从未接受过这些领域的正式培训，很少有研究人员拥有这种独特的跨学科专业知识。在该奖项的 K99 阶段，布劳恩博士将利用教程、研讨会/会议和教学指导来获得以下方面的额外培训：1) 内分泌学概念以及环境化学品对内分泌系统的影响； 2) 心理测试的选择、管理、验证和解释； 3）儿童神经发育。该培训将应用于一个原创研究项目，在该项目中，Braun 博士将在 Dr. Hauser 的环境与生殖健康 (EARTH) 研究的指导下，对 25 名儿童进行计算机化的视觉空间能力测试。豪瑟和贝林格。这些计算机化测试类似于莫里斯水迷宫和径向臂迷宫，用于神经毒性的动物研究。 利用这些新技能和前瞻性健康结果和环境测量 (HOME) 出生队列，布劳恩博士将在该奖项的 R00 阶段实现两个具体目标：1) 确定妊娠期 BPA/邻苯二甲酸盐暴露是否与视觉空间相关300 名儿童的能力以及性别是否改变了这些关联；2) 确定 330 名婴儿妊娠期 BPA/邻苯二甲酸盐暴露是否与胎粪性类固醇浓度相关。 布劳恩博士非常适合开展这项研究，因为他之前接受过培训，并且他的导师、顾问和机构提供了独特的资源。这项拟议的培训和研究将使他能够研究 EDC 对其他荷尔蒙系统的影响，以及它们是否会增加不良儿童行为结果的风险。 对性类固醇的检查将增进我们对 EDC 作用的潜在生物学机制的了解，并且使用动物类似物进行神经行为测试将改善流行病学和动物研究之间的比较。公共卫生相关性：神经行为障碍给教育和医疗资源带来巨大负担；因此，首要任务是了解与这些疾病相关的因素。拟议的研究可以通过解决我们在 BPA 和邻苯二甲酸盐神经毒性及其对人类神经行为影响的知识方面的重要研究空白，为公共卫生干预措施提供信息。 公共卫生相关性：胎儿可能容易受到双酚 A (BPA) 和邻苯二甲酸盐等内分泌干扰化合物的影响。 接触这些化合物可能会扰乱妊娠性类固醇代谢，从而损害儿童神经发育。该应用程序将使用内分泌干扰和儿童神经发育方面的综合培训计划，帮助 Joe M. Braun 博士开展高质量的研究，研究妊娠期 BPA/邻苯二甲酸盐暴露对胎儿性类固醇和儿童视觉空间能力的影响。