ASSESSING ADVERSE EFFECTS OF ENVIRONMENTAL HAZARDS ON REPRODUCTIVE HEALTH

评估环境危害对生殖健康的不利影响

• 批准号: 6664552
• 负责人: Bill Lee Lasley
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-24 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6664552
• 关键词: Macaca fascicularis; aromatic hydrocarbon receptor; bioassay; biomarker; chlorohydrocarbon; clinical research; dioxins; environmental exposure; environmental health; environmental toxicology; estrogen analog; estrogen receptors; female; female reproductive system disorder; food chain contamination; hazardous substances; human subject; human tissue; industrial waste; menstrual cycle; method development; toxicant screening; toxin

The objectives of this project are to develop and apply methods which can be used to identify and quantify xenobiotic substances in biological samples that act through the estrogen receptor (ER) and/or the aryl- hydrocarbon receptor (AhR) to cause adverse effects on human reproductive health. Specific Aim I will utilize cell-based bioassay systems developed in the Cellular Biology Project (Project 5) as the basis for methods to detect ER- and AhR agonists in biological samples following removal of endogenous (steroidal) estrogens which compete for ER binding. We hypothesize that endogenous ER binding ligands can be removed from serum prior to assay by immuno-precipitation. The bioassays will be tested using a unique set of paired serum and urine samples from a population of male Russian children with high levels of exposure to environmental chemicals. Specific Aim II employs the non- human primate model to validate the bioassay methods using blood and urine samples recovered following experimental in vivo exposures to TCDD, t-octylphenol, fenvalerate, atrazine and diuron1. We hypothesize that bioassays for bioactivators of the ER and AhR will be as sensitive as specific immunoassays (from the Immunochemical Biomarkers Project, Project 3) for detecting exogenous ER- and AhR agonists. Specific Aim II involves the application of previously developed assays for reproductive biomarkers and bioassays of exposure for study of a population of women who eat contaminated fish from the San Francisco Bay. Our preliminary data indicate that there are abnormalities of menstrual function in this group of women, and we hypothesize that exposure to xenobiotic ER agonists and AhR agonists is responsible. Specific Aim IV will utilize the same assays for study of a population of women with suspected exposure to chlorinated hydrocarbons who are recruited in the Epidemiology Project (Project 9). Specific Aim V will adapt existing immunoassays for reproductive hormone metabolites to a format which is more efficient for population-based studies. This aim relies on the Immunochemical Biomarkers Project (Project 3) for the development of critical reagents and the Biosensors Project (Project 8) for development of assay formats.

该项目的目标是开发和应用可用于识别和量化生物样品中的异生物质的方法，这些异生物质通过雌激素受体（ER）和/或芳烃受体（AhR）起作用，对人类造成不利影响。生殖健康。具体目标 I 将利用细胞生物学项目（项目 5）开发的基于细胞的生物测定系统，作为在去除竞争 ER 结合的内源（类固醇）雌激素后检测生物样品中 ER 和 AhR 激动剂的方法的基础。我们假设在通过免疫沉淀进行测定之前可以从血清中去除内源性 ER 结合配体。生物测定将使用一组独特的配对血清和尿液样本进行测试，这些样本来自大量接触环境化学物质的俄罗斯男性儿童。 Specific Aim II 采用非人类灵长类动物模型来验证生物测定方法，使用体内实验暴露于 TCDD、叔辛基苯酚、氰戊菊酯、莠去津和敌草隆 1 后回收的血液和尿液样本。我们假设 ER 和 AhR 生物激活剂的生物测定将与检测外源 ER 和 AhR 激动剂的特异性免疫测定（来自免疫化学生物标志物项目，项目 3）一样敏感。具体目标 II 涉及应用先前开发的生殖生物标志物测定法和暴露生物测定法，对食用旧金山湾受污染鱼类的妇女群体进行研究。我们的初步数据表明，这组女性存在月经功能异常，我们推测其原因是接触异生素 ER 激动剂和 AhR 激动剂。具体目标 IV 将利用相同的检测方法对流行病学项目（项目 9）中招募的疑似接触氯化碳氢化合物的女性群体进行研究。 Specific Aim V 将使现有的生殖激素代谢物免疫测定方法适应一种对基于人群的研究更有效的格式。这一目标依赖于用于开发关键试剂的免疫化学生物标志物项目（项目 3）和用于开发测定格式的生物传感器项目（项目 8）。