Preconception Nutrition, Endocrine Disruptors, Reproductive Outcomes

描述（由申请人提供）：二氯二苯三氯乙烷（DDT）及其代谢物包括二氯二苯二氯乙烯（DDE）是已知的内分泌干扰物。尽管滴滴涕在美国被禁止使用，但在一些国家，它仍被用于控制疟疾。滴滴涕/DDE仍然是一个公共卫生问题，因为这些化学品在生态系统中无处不在，并且由于其稳定性、亲脂性和在食物链中生物积累的倾向，在本底接触水平下可能对健康造成不利影响。本研究旨在验证孕前体重指数和微量营养素状况可以改变滴滴涕/DDE环境暴露与生殖结果之间关系的假设。本研究将利用现有的中国妇女队列，这些妇女在计划怀孕时被招募，并从孕前到妊娠终点进行前瞻性随访。通过之前的研究，我们获得了对这一建议至关重要的数据，包括：(1)生殖激素：妊娠二醇-3-葡萄糖醛酸盐（PdG）、雌酮缀合物（E1C）和人绒毛膜促性腺激素（b-hCG）在前瞻性观察月经周期的每日首次空尿样本中评估；(2)生殖结局：月经紊乱、激素功能障碍、受孕时间、早孕丢失（EPL）、自然流产（SAB）、出生结局（胎龄、出生体重、身长、头围）；(3)孕前BMI和微量营养素：包括叶酸、B6、B12、半胱氨酸、同型半胱氨酸、血红蛋白、铁蛋白和转铁蛋白受体（TfR）的血清生物标志物；(4)孕前暴露：包括血清DDT/DDE、HCB和PCB水平。我们建议深入的统计分析，以解决以下新的研究问题，这些问题不是以前资助的研究的一部分。目的1。母体孕前BMI是否可以改变DDT/DDE暴露与生殖结局之间的关系，包括：(1)激素功能障碍：雌激素分泌（REE）减少、无排卵、黄体期（ALP）异常和卵泡期（AFP）异常；(2)月经紊乱；(3)不孕;(4) EPL和SAB；(5)不良出生结局？目标2。孕妇孕前b族维生素状况能否改变目标1中概述的DDT/DDE暴露与生殖结果之间的关系？目标3。孕妇孕前铁状况能否改变目标1中概述的滴滴涕/DDE暴露与生殖结果之间的关系？目标4。孕前体重指数、微量营养素和滴滴涕/DDE是否会共同影响目标1中概述的生殖结果？本研究结果将有助于我们进一步了解孕前BMI、微量营养素和DDT/DDE对健康的影响及其共同作用，并为未来其他营养素和内分泌活性化合物的研究提供模型，为制定孕前营养预防策略以减轻环境化学物质暴露对生殖结果的有害影响奠定基础。

DESCRIPTION (provided by applicant): Dichlorodiphenyl trichloroethane (DDT) and its metabolites including dichlorodiphenyl dichloroethene (DDE) are known endocrine disruptors. Although DDT was banned in the US, it is still used in some countries for malaria control. DDT/DDE remain a public health concern because these chemicals are omnipresent in the ecosystem and may cause adverse health effects at background levels of exposure as a result of their stability, lipophilic nature, and propensity to bioaccumulate in the food chain. This proposal aims to test the hypotheses that preconception BMI and micronutrient status can modify the relationships between environmental exposure to DDT/DDE and reproductive outcomes. This study will utilize an existing cohort of Chinese women who were recruited when they planned to conceive and were prospectively followed from preconception to pregnancy endpoints. Through previous studies, we have obtained data critical to this proposal, including (1) Reproductive Hormones: pregnanediol-3-glucuronide (PdG), estrone conjugate (E1C), and human chorionic gonadotropin (b-hCG) assessed in daily first void urine samples of prospectively observed menstrual cycles; (2) Reproductive Outcomes: menstrual disturbance, hormone dysfunction, time to conception, early pregnancy loss (EPL), spontaneous abortion (SAB), and birth outcomes (gestational age, birth weight, length, and head circumference); (3) Preconception BMI and Micronutrients: including serum biomarkers of folate, B6, B12, cysteine, homocysteine, hemoglobin, ferritin, and trans-ferritin receptor, TfR; and (4) Preconception Exposure: including serum DDT/DDE, HCB, and PCB levels. We propose in-depth statistical analyses to address the following new research questions that were not part of the previously funded studies. Aim 1. Can maternal preconception BMI modify the associations between exposure to DDT/DDE and reproductive outcomes, including (1) hormone dysfunction: reduced estrogen excretion (REE), anovulation, abnormal luteal phase (ALP), and abnormal follicular phase (AFP); (2) menstrual disorders; (3) infertility; (4) EPL and SAB; and (5) adverse birth outcomes? Aim 2. Can maternal preconception B-vitamin status modify the associations between exposure to DDT/DDE and reproductive outcomes outlined in Aim 1? Aim 3. Can maternal preconception iron status modify the associations between exposure to DDT/DDE and the reproductive outcomes outlined in Aim 1? Aim 4. Can preconception BMI, micronutrients and DDT/DDE jointly affect the reproductive outcomes outlined in Aim 1? Findings from this study will improve our understanding of the health effects and joint action of preconception BMI, micronutrients, and DDT/DDE, and provide a model for future studies of other nutrients and endocrinologically-active compounds, and lay a foundation for the development of preconception nutritional prevention strategies to mitigate the harmful effects of environmental chemical exposures on reproductive outcomes.