This proposal responds to RFA OH-01-001 """"""""Endocrine Disruptors: Epidemiologic Approaches."""""""" Both animal and in vitro studies support the hypothesis that dichlorodiphenyl trichloroethane (DDT) and its metabolites are potentially important human reproductive toxins. However, the epidemiologic data associating DDT with human reproductive health are limited. The goal of this proposal is to establish a dose-response relationship between exposure to dichlorodiphenyl dichloroethene (DDE), a major and stable metabolite of DDT, endocrine dysfunction, and adverse reproductive outcomes in women. We will test the hypotheses that exposure to DDE is associated with (1) hormone dysfunction including reduced estrogen excretion (REE), anovulation, abnormal luteal phase (ALP), and abnormal follicular phase (AFP); (2) menstrual disorders; (3) reduced fecundability; and (4) adverse pregnancy outcomes including spontaneous abortion (SAB), preterm delivery, low birth weight, and intrauterine growth retardation (IUGR). We will further test the hypotheses that endocrine disruption evaluated by REE, anovulation, ALP, and AFP is associated with above adverse reproductive outcomes. This proposal is built on a large prospective cohort study in Anqing, China, funded by NICHD (HD32505, period: 1996-2001) to evaluate the effects of rotating shift work on reproductive outcomes. A total of 1,200 married women employees of Anqing Textile Mill who were between 20 and 34 years of age, never smokers, and who obtained permission to have a child and attempted to become pregnant over the course of the study have been enrolled in the parent study. Information available from this cohort includes: (1) detailed baseline and follow-up questionnaires on sociodemographic characteristics, reproductive history, occupational and environmental factors, and dietary intake; (2) daily diary from each woman reporting menstruation, use of medications, sexual intercourse, contraceptive use, active and passive smoking, alcohol use, and occupational exposure; (3) clinical data on reproductive outcomes, including menstrual disturbances, time to conception, SAB, preterm delivery, low birth weight, and IUGR; (4) daily urine samples from each woman for up to one year or until pregnancy is clinically confirmed; (5) measures of time to conception and subclinical fetal loss determined by a highly sensitive and specific assay for urinary B-hCG; and (6) archived pre-pregnant plasma samples from each woman. This proposal will include the 1,200 women already enrolled in the parent study. Plasma DDT/DDE levels will be measured and urinary pregnanediao-3-glucorinide (PdG), estrogen conjugates (E1C), and follicle stimulating hormone (FSH) will be analyzed. These newly obtained pesticide and hormone data will be linked to existent epidemiologic and clinical database to investigate dose-response relationships between DDE exposure, hormone dysfunction, and adverse reproductive outcomes, with adjustment for important confounders.
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