ORGANOPHOSPHATE PESTICIDES AND HUMAN REPRODUCTIVE HEALTH

有机磷酸酯农药与人类生殖健康

• 批准号: 6197401
• 负责人: XIPING XU
• 金额: $ 51.65万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6197401
• 关键词: China; agriculture worker; clinical research; environmental exposure; environmental health; environmental toxicology; estrogens; gene environment interaction; hormone regulation /control mechanism; human subject; interview; menstrual cycle disorder; organophosphorus insecticide; pregnancy; reproductive system disorder; sperm analysis

DESCRIPTION: (Adapted from the Investigator's Abstract) This study is designed to recruit and prospectively follow a cohort of women and their husbands to assess the effects of exposure to organophosphate (OP) pesticides on adverse reproductive outcomes in both men and women in agricultural workers. Married never-smoking women age 20-34 who currently work in Haikou Township, Anqing, who have obtained permission to have a child, and who will be attempting to become pregnant over the course of the study will be eligible for the study. Reproductive endpoints will include (1) semen parameters (concentration, total count, motility, progression and morphology), (2) menstrual disorders (oligomenorrhea, amenorrhea, polymenorrhea, intermenstrual bleeding, prolonged menstrual bleeding, dysmenorrhea, and irregular menstruation); (3) alterations in hormone patterns including reduced estrogen excretion (REE), anovulation, abnormal luteal phase (ALP), and abnormal follicular phase (AFP) in women and abnormalities of LH, FSH, TSH, SHBG, inhibin-B and testosterone in men; (4) fecundability; and (5) pregnancy outcomes including spontaneous abortion, preterm delivery, low birth weight and intrauterine growth retardation. After enrollment, interviewers will administer a previously validated questionnaire to the women and their husbands to collect baseline information on sociodemographic, environmental, occupational, and personal covariates. Semen samples will be obtained by trained technicians at enrollment and again four months later. Each woman will keep a diary of her menstrual information, environmental exposures, and dietary intake. Daily urine samples will be collected from each female subject for up to one year or until a pregnancy occurs. Urinary PdG, EIC, LH, FSH and hCG will be measured to identify abnormal endocrine patterns and subclinical pregnancy. Once a woman becomes pregnant, she will be followed for pregnancy outcomes obtained from a follow-up survey and hospital records where the baby is delivered. Extensive exposure assessment will be conducted throughout the follow-up period and, therefore, dose-response relationships can be established. All participants will keep daily exposure diaries. Urine samples will be measured for metabolites on selected exposure days. A subset of participants will be studied for personal air monitoring and serial analysis of urine metabolites to validate the exposure diary and urine metabolite assay. The investigators state that the proposed study has several strengths: (1) it will be conducted in a population with a broad range of organophosphate pesticide exposure; (2) exposure will be well-characterized; (3) each woman and her husband will be studied simultaneously; (4) the prospective study design can eliminate certain flaws or potential biases in previous retrospective studies; (5) time to conception and spontaneous abortion will be evaluated with the improved specific hCG assay, which can detect pregnancy within a few days of implantation; (6) recently-developed biomarkers, including urinary hormone assays and FISH methods, will be applied to the study; (7) gene-environment interactions will be tested; (8) the field cost in China is much lower than that in the U.S.; and (9) the population possesses unique characteristics for examining the proposed hypothesis, i.e., a stable workforce, a non-smoking group and excellent compliance rates.

描述：（改编自研究者摘要）本研究旨在 招募并前瞻性地跟踪一组妇女及其丈夫， 评估接触有机磷农药对有害生物的影响 农业工人中男女的生殖结果。结婚 目前在安庆市海口镇工作的20-34岁从不吸烟的女性， 谁获得了生孩子的许可，谁将试图 在研究过程中怀孕的妇女将有资格参加本研究。 生殖终点将包括（1）精液参数（浓度，总 计数、运动、进展和形态），（2）月经紊乱 （月经过少，闭经，月经过多，经间期出血， 月经出血、痛经、月经不调）;（3）改变 在激素模式中，包括雌激素排泄减少（REE），不排卵， 女性黄体期异常（ALP）和卵泡期异常（AFP）， 男性LH、FSH、TSH、SHBG、B-B、睾酮异常;（4） 生育能力;和（5）妊娠结果，包括自然流产， 早产、低出生体重和宫内发育迟缓。后 入组后，面试官将管理一份先前验证过的问卷 妇女及其丈夫收集基线信息， 社会人口统计学、环境、职业和个人协变量。精液 样本将由经过培训的技术人员在入组时获得， 月后每位女性都将自己的月经信息记录在日记中， 环境暴露和饮食摄入。每天的尿液样本将 从每例女性受试者中采集长达一年或直至妊娠 发生。将测量尿PdG、EIC、LH、FSH和hCG，以识别异常 内分泌模式和亚临床妊娠。一旦女性怀孕， 她将接受随访调查获得的妊娠结局 以及孩子出生的医院记录广泛的暴露评估 将在整个随访期间进行，因此， 可以建立关系。所有参与者将保持每日接触 日记。将在选定暴露条件下测量尿液样本中的代谢物 天将对一部分参与者进行个人空气监测， 尿液代谢物的系列分析，以验证暴露日志和尿液 代谢物测定。研究人员指出，这项研究有几个 优点：（1）它将在具有广泛的 有机磷农药暴露;（2）暴露将得到充分表征; (3)每个女人和她的丈夫将同时研究;（4） 前瞻性研究设计可以消除某些缺陷或潜在的偏见， 既往回顾性研究;（5）受孕时间和自然流产 将用改进的特异性hCG测定法进行评估，该测定法可以检测 在植入后几天内怀孕;（6）最近开发的生物标志物， 包括尿激素测定和FISH方法，将应用于 研究;（7）基因与环境的相互作用将被测试;（8）实地成本， 中国比美国低得多;（9）人口拥有 用于检查所提出的假设的独特特征，即，稳定的 员工队伍、非吸烟群体和出色的合规率。