Preconception Nutrition, Endocrine Disruptors, Reproductive Outcomes

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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.