Prenatal Organochlorine Exposure and Male Reproduction

描述（由申请人提供）：尽管最近对精子数量下降的说法感到担忧，但几乎没有（如果有的话）流行病学证据表明与环境暴露或暴露时间有关。男性生殖功能紊乱，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。迄今为止，没有直接的人体证据支持或反驳这一猜想。在子宫和/或儿童早期接触这些化学物质可能会破坏睾丸发育或相关内分泌途径的发育，导致男性生殖功能的轻微破坏。我们建议研究产前暴露于一类内分泌干扰物（有机氯化合物）与成年男性睾丸和内分泌功能（包括精液质量、生育潜力、当前激素浓度和怀孕时间）之间的关系。我们还建议检查是否这种关联，如果有的话，是由母体甲状腺功能的破坏介导的。通过对国家围产期合作项目和儿童健康与发展研究的哥伦比亚-长老会队列的成年成员进行随访，我们将获得关于生育史、当前生活方式、社会经济地位和病史的问卷数据，要求受试者采集血液样本，并要求受试者间隔约3周到诊所采集两次精液样本。精液样本将在加州大学戴维斯分校按照标准程序进行分析。检测血清中睾酮、雌二醇、促卵泡激素、黄体生成素和抑制素b的含量。检测保存、冷冻的产前血清中有机氯化合物、游离甲状腺素、促甲状腺激素和甲状腺过氧化物酶抗体的含量。统计分析将评估有机氯化合物（总和在二级分析中作为特定同源物或同源物组）与每个结果变量之间的关联。其他分析将评估怀孕期间母亲甲状腺功能是否减轻这些关联。这项研究首次对产前暴露于有机氯化合物和男性生殖进行了大规模系统评估，对基础科学、公共卫生和公共政策具有重要意义。

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.