Prenatal Organochlorine Exposure and Male Reproduction

产前有机氯暴露与男性生殖

• 批准号: 6777919
• 负责人: Pam R Factor-Litvak
• 金额: $ 52.01万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-07 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6777919
• 关键词: adult human (21+); chlorohydrocarbon insecticide; clinical research; early experience; embryo /fetus toxicology; fertility; hormone inhibitor; hormone regulation /control mechanism; human subject; lifestyle; longitudinal human study; male; male reproductive system disorder; questionnaires; sex development disorder; sperm analysis; statistics /biometry

DESCRIPTION (provided by applicant): Despite recent concern over the purported decline in sperm counts, there is little, if any, epidemiologic evidence regarding associations with environmental exposures or the timing of such exposures. Disruption of male reproductive function, and in particular decreased semen quality, is thought to be associated with exposure to endocrine active chemicals. To date, no direct evidence in humans either supports or refutes this conjecture. It is possible that exposure to such chemicals in utero and/or during early childhood may disrupt testicular development or development of related endocrine pathways, resulting in subtle disruption of male reproductive function. We propose to examine associations between prenatal exposures to one class of endocrine disruptors, the organochlorine compounds, and testicular and endocrine function in adult men including semen quality, fertility potential, current hormone concentrations and time to pregnancy. We also propose to examine whether such associations, if any, are mediated by disruptions of maternal thyroid function. From a follow up of the now adult members of the Columbia-Presbyterian cohort of the National Collaborative Perinatal Project and the Child Health and Development Study, we will obtain questionnaire data on fertility history, current lifestyle, socioeconomic status, and medical history, request a blood sample and request that the subject come to the clinic for two semen samples, approximately 3 weeks apart. Semen samples will be analyzed using a standard protocol at the University of California, Davis. Serum will be assayed for testosterone, estradiol, follicle stimulating hormone, luteinizing hormone and inhibin B. Stored, frozen prenatal sera will be assayed for organochlorine compounds, and for free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies. Statistical analysis will assess the associations between organochlorine compounds (total and in secondary analyses as specific congeners or groups of congeners) and each outcome variable. Other analyses will assess whether maternal thyroid function during pregnancy mitigates these associations. This study represents the first large systematic evaluation of prenatal exposures to organochlorine compounds and male reproduction and has important implications for basic science, public health and public policy.

描述（由申请人提供）：尽管最近对精子计数下降的担忧，但关于与环境暴露或此类暴露时间相关的流行病学证据很少（如果有的话）。男性生殖功能的破坏，特别是精液质量下降，被认为与接触内分泌活性化学物质有关。到目前为止，在人类身上没有直接的证据支持或反驳这一猜想。在子宫内和（或）幼儿期接触此类化学品可能会破坏睾丸发育或相关内分泌途径的发育，从而导致男性生殖功能的微妙破坏。我们建议检查产前暴露于一类内分泌干扰物，有机氯化合物，睾丸和内分泌功能的成年男性，包括精液质量，生育能力，目前的激素浓度和怀孕时间之间的关联。我们还建议检查这种关联，如果有的话，是否介导的母体甲状腺功能的中断。 从国家围产期合作项目和儿童健康与发育研究的哥伦比亚长老会队列的成年成员的随访中，我们将获得有关生育史，当前生活方式，社会经济状况和病史的问卷数据，要求血液样本，并要求受试者到诊所接受两次精液样本，间隔约3周。精液样本将在加州大学戴维斯分校使用标准方案进行分析。将测定血清中的睾酮、雌二醇、促卵泡激素、促黄体生成素和卵泡抑素B。将对储存、冷冻的产前血清进行有机氯化合物、游离甲状腺素、促甲状腺激素和甲状腺过氧化物酶抗体检测。统计分析将评估有机氯化合物（总体和次级分析中作为特定同系物或同系物组）与每个结果变量之间的关联。其他分析将评估孕妇在怀孕期间的甲状腺功能是否减轻了这些关联。 这项研究是首次对产前接触有机氯化合物和男性生殖进行大规模系统评估，对基础科学、公共卫生和公共政策具有重要意义。