The investigators propose a targeted investigation of endocrine-related outcomes in individuals in the Michigan PBB Registry and their offspring to follow up intriguing findings of a study recently completed by this team. In 1973, inadvertent substitution of a livestock feed supplement with fire retardant led to widespread contamination of meat and dairy products in Michigan with polybrominated biphenyls (PBBs), a class of chemicals toxicologically similar to PCBs, PBDE, DDE and other halogenated organics suspected to disrupt endocrine function. Over 4000 individuals with high likelihood of exposure were subsequently enrolled into the Michigan PBB Registry, and serum samples were analyzed for PBB. The proposers recently completed a twenty-year follow up survey of women in the registry regarding occurrence of endocrine-related outcomes, and the current application will pursue key findings of this survey as follows. The observation of an association of perinatal PBB exposure with reduced age at menarche in the daughters of registry participants will be followed up in two ways: 1) an expanded assessment of ovarian function in a subgroup of the daughters, using menstrual diaries and hormonal assays of daily urine samples (50 high exposure, 50 low exposure), and 2) an investigation of pubertal development in the sons of women in the registry to assess whether analogous impacts on pubertal development are observed in the boys, using a questionnaire assessment of Tanner stages and other pubertal landmarks in sons less than 18 years of age (n=204). The suggestion of an excessive spontaneous abortion rate among the exposed daughters of reproductive age will be followed up by: 1) updating the reproductive histories of the daughters over age 18 (n=214), and 2) by determining reproductive success in the sons over 18 years of age (n=218). Finally, the finding of altered menstrual cycle characteristics among the women in the registry will, be pursued by performing a menstrual diary and urinary hormone study in the adult women (50 high exposure, 50 low exposure) similar to that proposed for the daughters. Each of the proposed investigations allows targeted, efficient follow up of the important findings observed in the previous study, and will provide further insight into possible impacts of this class of chemicals on pubertal development, reproductive health and ovarian function.
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