Prenatal Organochlorine Exposure and Male Reproduction

描述(由申请人提供)：尽管最近人们对据称的精子数量下降感到担忧，但几乎没有流行病学证据表明与环境暴露或这种暴露的时间有关。男性生殖功能的中断，特别是精液质量的下降，被认为与接触内分泌活性化学物质有关。到目前为止，还没有直接的人类证据支持或驳斥这一猜测。在子宫和/或儿童早期接触这种化学物质可能会扰乱睾丸发育或相关内分泌途径的发育，导致男性生殖功能的微妙中断。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与成年男性的睾丸和内分泌功能之间的关系，包括精液质量、生育潜力、当前激素浓度和怀孕时间。我们还建议研究这种关联是否由母体甲状腺功能的紊乱所调节。通过对哥伦比亚-长老会国家合作围产期项目和儿童健康与发展研究的成年成员的跟踪调查，我们将获得关于生育史、当前生活方式、社会经济状况和病史的问卷数据，要求采集血液样本，并要求受试者来诊所采集两份精液样本，大约相隔3周。精液样本将在加州大学戴维斯分校使用标准程序进行分析。将检测血清中的睾酮、雌二醇、卵泡刺激素、黄体生成素和抑制素B。储存、冷冻的产前血清将检测有机氯化合物，以及游离甲状腺素、促甲状腺激素和甲状腺过氧化物酶抗体。统计分析将评估有机氯化合物(总的和在二次分析中作为特定的同系物或同系物组)与每个结果变量之间的联系。其他分析将评估怀孕期间母亲的甲状腺功能是否减轻了这些联系。这项研究是对产前接触有机氯化合物和男性生殖的第一次大规模系统评估，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.