Maternal Pesticide Exposure and Pregnancy Outcomes

描述（由申请人提供）：虽然多氯联苯（PCB）和许多氯化农药（包括滴滴涕）的使用现在已被禁止或限制，但人们仍然担心它们对人类健康的潜在影响，因为它们持久存在于环境中，集中在食物链中，并储存在脂肪组织中。实验室研究表明，环境相关水平的多氯联苯和氯化农药通过扰乱胚胎发育的机制与不孕和流产有关。流行病学研究报告了 PCB 和 DDE（稳定 DDT 代谢物）与流产的关联。在拟议的研究中，我们将探讨氯化化合物对接受体外受精（IVF）的女性的发育毒性，这可以用作评估通常无法观察到的早期发育的模型。将测量的发育终点包括卵母细胞产生、受精以及植入前和植入后胚胎发育。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丢失（自然流产和死产）和围产期结局，例如出生体重。拟议的研究具有成本效益，因为它使用了最近完成的 NICHD 资助的一项关于 IVF 成功的流行病学预测因素的多中心研究的数据和样本。在这项多中心研究中，有 2494 对夫妇在 1994 年至 2003 年间经历了 5071 个 IVF 周期的数据。从女性伴侣处收集并存档了血清和卵巢卵泡液，并将用于测量 PCB 和氯化农药，如 DDE、六氯苯、灭蚁灵以及氯丹代谢物、反式九氯丹和氯丹。受试者完成了详细的健康和生活方式调查问卷，并从患者病历中提取了有关体外受精方案和妊娠结局的信息。该研究设计新颖，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，早期发育失败在临床上表现为不孕和早期流产。早期发育失败占妊娠损失的大部分，被认为是对多氯联苯和氯化农药接触最敏感的发育阶段。由于不孕症和早期妊娠流产的病因在很大程度上仍无法解释，因此识别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.