Preconception Nutrition, Endocrine Disruptors, Reproductive Outcomes

描述（由申请人提供）：已知二氯二苯三氯乙烷（DDT）及其代谢物（包括二氯二苯二氯乙烯（DDE））是内分泌干扰物。虽然DDT在美国被禁止使用，但在一些国家仍被用于疟疾控制。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，由于其稳定性、亲脂性和在食物链中生物累积的倾向，在背景接触水平下可能对健康造成不利影响。该提案旨在检验孕前BMI和微量营养素状况可以改变环境暴露于DDT/DDE和生殖结果之间的关系的假设。本研究将利用计划怀孕时招募的现有中国女性队列，并从孕前至妊娠终点进行前瞻性随访。通过先前的研究，我们获得了对该提议至关重要的数据，包括（1）生殖激素：在前瞻性观察的月经周期的每日首次排尿尿液样本中评估的孕激素-3-葡萄糖醛酸苷（PdG）、雌酮结合物（E1 C）和人绒毛膜促性腺激素（b-hCG）;（2）生殖结局：月经紊乱、激素功能障碍、受孕时间、早期妊娠丢失（EPL）、自然流产（SAB）和分娩结局（3）孕前体重指数（BMI）和营养素：包括血清叶酸、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）;（4）孕前暴露：包括血清中DDT/DDE、HCB和PCB水平。我们提出了深入的统计分析，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。目标1。母亲孕前BMI是否可以改变暴露于DDT/DDE与生殖结局之间的关联，包括（1）激素功能障碍：雌激素排泄减少（REE）、无排卵、异常黄体期（ALP）和异常卵泡期（AFP）;（2）月经紊乱;（3）不孕症;（4）EPL和SAB;（5）不良出生结局？目标2.母亲孕前B族维生素状况是否可以改变目标1中概述的滴滴涕/DDE暴露与生殖结果之间的关联？目标3.母亲孕前铁状况能否改变目标1中所述的暴露于DDT/DDE与生殖结果之间的关联？目标4。孕前BMI、微量营养素和DDT/DDE是否会共同影响目标1中概述的生殖结果？这项研究的结果将提高我们对孕前BMI，微量营养素和DDT/DDE的健康影响和联合作用的理解，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，并为制定孕前营养预防策略以减轻环境化学品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.