BIOMARKERS FOR HUMAN REPRODUCTIVE EPIDEMIOLOGY

University Of California Davis, Davis CA

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Abstract

This project will utilize exposure data and samples previously collected in three large prospective studies on reproductive health in China. Our objective is to investigate the adverse effects of environmentally-induced perturbations during specific stages of the menstrual cycle. The major outcomes of interest include prolonged follicular, decreased estrogen secretion, increased bone loss and decreased fecundability. The study will use all eligible cycles from 1,200 women in a rotating shift work study to demonstrate the following: changes in urinary FSH metabolites in the late luteal phase can predict a long follicular phase in the subsequent cycle; a long follicular phase is associated with lower daily excretion of estrone conjugates. In the first five days of the cycle, higher excretion of urinary bone markers throughout the follicular phase and lower conception rates compared to a normal length follicular phase; work shift changes in the preceding luteal phase are associated with a long follicular phase, low estrogen excretion, increased bone resorption and low fecundability. Additional samples from 600 women in petrochemical study and 800 women in lead study combined with the subjects from the rotating shift work study will be analyzed to demonstrate the following: among non- exposed subjects a significant increase in the urinary hCG B:I ration during the week following pregnancy detection will be observed in surviving pregnancies compared to failing pregnancies in which the hCG B:I ratio will not change; and of the women with failing pregnancies, those exposed to an environmental hazard are more likely to experience a significant increase in the B:I ratio during the week following pregnancy detection than are the unexposed, and there will be a significant decline in the hCG B:I ratio over a period of several days prior to termination of the pregnancy compared with surviving large sample source; (2) several recently developed biomarkers will be applied to elucidate the biological mechanisms involved in adverse reproductive outcomes; (3) shift work, which is an objective measurement and should be free of measurement error, will be used to test several of our proposed hypotheses; (4) the prospective study design can eliminate flaws or potential biases that can confound retrospective studies; and (5) this study can serve as a paradigm to study the biological mechanisms of other reproductive risk.