Preconception Nutrition, Endocrine Disruptors, Reproductive Outcomes

孕前营养、内分泌干扰物、生殖结果

• 批准号: 8487539
• 负责人: XIAOBIN WANG
• 金额: $ 8.1万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-21 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487539
• 关键词: Address; Affect; Age; Anemia; Animals; Anovulation; Attenuated; Biological Markers; Birth; Birth Weight; Body mass index; Chemicals; Chinese People; Clinical; Complex; Conceptions; Country; Cysteine; Data; Databases; Development; Dietary Intervention; Dose; Ecosystem; Endocrine Disruptors; Environmental Exposure; Epidemiologic Studies; Epidemiology; Estrogens; Excretory function; Exposure to; Ferritin; Folate; Food Chain; Foundations; Functional disorder; Funding; Future; Gestational Age; Head circumference; Health; Hemoglobin; Hexachlorobenzene; High Prevalence; Homocysteine; Homocystine; Hormones; Human; Human Chorionic Gonadotropin; Individual; Infertility; Intervention; Iron; Joints; Length; Luteal Phase; Malaria; Maternal Exposure; Menarche; Menstrual cycle; Menstruation Disturbances; Micronutrients; Modeling; National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; Nature; Nutrient; Nutritional; Outcome; Polychlorinated Biphenyls; Predisposition; Pregnancy; Pregnancy Outcome; Pregnancy loss; Pregnanediol; Prevention strategy; Public Health; Recruitment Activity; Reproductive Health; Research; Sampling; Series; Serum; Spontaneous abortion; Testing; Time; Toxin; Trichloroethanes; Urine; Variant; Vitamin B Complex; Vitamin B Deficiency; Woman; Work; cohort; environmental chemical exposure; estrone-3-glucuronide; ferritin receptor; improved; iron deficiency; mother nutrition; nutrition; predictive modeling; proliferative phase Menstrual cycle; public health relevance; reproductive; reproductive hormone; response

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.

描述（由申请人提供）：二氯二苯三氯乙烷（DDT）及其代谢物，包括二氯苯基二氯乙烯（DDE）是已知的内分泌干扰物。尽管在美国被禁止使用DDT，但仍在某些国家使用它来控制疟疾。 DDT/DDE仍然是公共健康问题，因为这些化学物质在生态系统中无所不在，并且由于其稳定性，亲脂性和在食物链中生物蓄积的倾向，可能在接触背景水平上引起不利的健康影响。该提案旨在检验先入为主的BMI和微量营养素状态可以改变环境暴露于DDT/DDE和生殖结果之间的关系。这项研究将利用现有的中国妇女队列，这些中国妇女计划构想，并从孕前到怀孕终点。通过先前的研究，我们获得了对该提案至关重要的数据，包括（1）生殖激素：妊娠-3-葡萄糖苷（PDG）（PDG），雌酮结合物（E1C）和人类绒毛膜促性腺激素（B-HCG）在每天的第一次效率的尿液样本中评估了前瞻性尿液样本。 （2）生殖结果：月经障碍，激素功能障碍，受孕时间，早期妊娠丧失（EPL），自发流产（SAB）和出生结果（胎龄，出生年龄，出生体重，长度和头圆周）； （3）染色的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，铁蛋白和跨性铁蛋白受体的血清生物标志物，TFR； （4）预选暴露：包括血清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，这些问题不是先前资助的研究的一部分。 AIM 1。孕产妇的先入BMI可以修改暴露于DDT/DDE和生殖结果之间的关联，包括（1）激素功能障碍：减少雌激素的排泄（REE），电卵形，异常露露相（ALP）和卵泡卵形相（异常卵泡相）（ABNormal foleal阶段）； （2）月经疾病； （3）不育； （4）EPL和SAB； （5）不利的出生结果？目的2。产妇先入为主的b-vitamin状态是否可以改变AIM 1中概述的DDT/DDE和生殖结果之间的关联？目的3。产妇的先入铁状态是否可以修改接触DDT/DDE与AIM 1中概述的生殖结果之间的关联？ AIM 4。先前的BMI，微量营养素和DDT/DDE可以共同影响AIM 1中概述的生殖结果吗？这项研究的结果将提高我们对牙6，微量营养素和DDT/DDE的健康影响和联合作用的理解，并为未来的其他营养和内分泌学上活性化合物的研究提供了模型，并为降低了对环境化学成分的损害化学作用的发展策略的发展奠定了基础。