Project Summary (2010-2015)

The over-arching objectives of this project are to develop and apply biomarker assays for evaluating human reproductive health at the population level. Risk to reproductive health is an area of growing public concern. Initially, this project focuses on the development of biomarker assays that can be applied to non-clinical situations and permit epidemiological studies to include prospective evaluations of individual women's reproductive health. The same biomarker assays validated for use in humans are also validated for use in the nonhuman primate animal model because the species-specific aspects of human reproduction often require the use of the laboratory macaque. These assays are then used to conduct in vivo experiments using the non-human primate animal model to fill important gaps in our understanding of specific environmental toxicants including targets of toxicity and exposure risks. The development of biomarkers for effect has subsequently led to the development and validation of biomarker assays for exposure to reproductive health risks and the identification of new environmental toxicants. All assays are adapted to automated platforms so that they are immediately available for use in all research and clinical centers, in vivo experiments conducted to confirm and characterize newly identified reproductive hazards and in vitro experiments using human cells lines are used to develop a deeper understanding of their mechanism(s) of action. Whenever possible, archival biological samples from previous or concurrent epidemiological studies are used in order to pose population-based queries that otherwise could not be addressed within the budget of a single project. Cooperation and collaboration with other projects is emphasized.

In Aim 4, structure activity relationships being established for a series of brominated flame retardants and their metabolites and the antimicrobial agent triclosan for their ability to alter ryanodine receptor signaling functions and the resulting impact on neuron growth and plasticity. In this Aim, integrated bioassay/biomarkers are being used to identify and characterize the biochemical and toxicological effects of individual chemicals and complex mixtures of chemicals.