Maternal Pesticide Exposure and Pregnancy Outcomes

描述（由申请人提供）：尽管多氯联苯（PCBs）和许多氯化农药（包括滴滴涕）的使用现已被禁止或限制，但由于它们在环境中持续存在，在食物链中集中，并储存在脂肪组织中，因此对其对人类健康的潜在影响仍存在担忧。实验室研究表明，多氯联苯和氯化农药的环境相关水平通过破坏胚胎发育的机制与不孕症和流产有关。流行病学研究报告多氯联苯和DDE（稳定的滴滴涕代谢物）与妊娠流产有关。在拟议的研究中，我们将探讨氯代化合物对体外受精（IVF）妇女的发育毒性，这可以作为评估早期发育的模型，通常是不可观察的。将测量的发育终点包括卵母细胞的产生、受精以及胚胎着床前后的发育。这些发育阶段的失败会导致不孕和流产。其他测量的终点包括临床妊娠损失（自然流产和死胎）和围产期结局，如出生体重。拟议的研究具有成本效益，因为它使用的数据和标本来自最近完成的NICHD资助的IVF成功流行病学预测的多中心研究。在这项多中心研究中，有2494对夫妇的数据，他们在1994年至2003年间进行了5071次试管婴儿周期。收集女性伴侣的血清和卵巢卵泡液并将其存档，用于测量多氯联苯和氯化农药（如DDE、六氯苯、灭螨）以及氯丹代谢物、反式壬氯胺和氧氯丹。受试者完成了详细的健康和生活方式问卷调查，并从患者病历中提取了体外受精方案和妊娠结局的信息。这项研究的设计是新颖的，因为它使用体外受精作为模型系统来研究多氯联苯和氯化农药与早期发育失败的关系，其临床表现为不孕和早期妊娠流产。早期发育失败代表了大多数妊娠损失，并且被认为是对多氯联苯和氯化农药暴露最敏感的发育阶段。由于不孕症和早孕流产的病因在很大程度上仍然不明，因此确定潜在的环境风险因素将具有重大的公共卫生意义。

DESCRIPTION (provided by applicant): Although the use of polychlorinated biphenyls (PCBs) and many of the chlorinated pesticides, including DDT, are now prohibited or restricted, there remains concern over their potential human health effects because they persist in the environment, concentrate up the food chain, and are stored in adipose tissue. Laboratory studies show associations of environmentally relevant levels of PCBs and chlorinated pesticides with infertility and pregnancy loss through mechanisms that disrupt embryo development. Epidemiologic studies report associations of PCBs and DDE (stable DDT metabolite) with pregnancy loss. In the proposed study, we will explore the developmental toxicity of chlorinated compounds in women undergoing in vitro fertilization (IVF), which can be used as a model to assess early development, normally unobservable. Developmental endpoints that will be measured include oocyte production, fertilization, and pre- and post-implantation embryo development. Failure at these developmental stages results in infertility and pregnancy loss. Other measured endpoints include clinical pregnancy loss (spontaneous miscarriage and stillbirth) and peri-natal outcomes, such as birth weight. The proposed study is cost-effective because it uses data and specimens from a recently completed NICHD funded multi-center study on epidemiologic predictors of IVF success. In the multi-center study there is data on 2494 couples undergoing 5071 IVF cycles between 1994 and 2003. Serum and ovarian follicular fluid were collected and archived from the female partner and will be used to measure PCBs and chlorinated pesticides such as DDE, hexachlorobenzene, mirex, and the chlordane metabolites, trans-nonachlor and oxychlordane. Subjects completed detailed health and lifestyle questionnaires and information on IVF protocols and pregnancy outcomes were abstracted from patient medical records. The study design is novel because it uses IVF as a model system to study the associations of PCBs and chlorinated pesticides with failure of early development, which manifests clinically as infertility and early pregnancy loss. Early developmental failure represents the majority of losses of pregnancy and is considered the most sensitive developmental stage to PCB and chlorinated pesticide exposure. Since the etiology of infertility and early pregnancy loss remains largely unexplained, the identification of potential environmental risk factors will have large public health significance.