Project 6
Assessing the Adverse Effects of Environmental Hazards on the Reproductive Health in Human Populations

Bill L. Lasley, Project Leader
Jiangang Chen, Senior Investigator

The first objective of this Project is to screen selected environmental contaminants for adverse effects on the human placenta. A primary cell culture of human trophoblast cells will be used to determine if compounds of interest from other projects are candidates for more intense investigations as determined by their ability to target placenta cells in vitro. This system has been successfully used for dioxin and bromodichloromethane and provides an incisive method for evaluating potential placental toxicants. The compounds to be investigated will be selected based on the results of Projects 1 and 2 in which human exposures and potential adverse effects, respectively, have been documented. The second objective will follow up the positive in vitro results with in vivo experiments using nonhuman primate animal model. These in vivo studies will confirm the previous in vitro results and verify the target of toxicity in a human-relevant animal model. The third and fourth objectives are to adapt existing biomarker immunoassays to an automated platform and develop new biomarker assays in conjunction with Project 5 and Core A. The new biomarkers for development, inhibin and activin, have been selected based on our perceived need to have a complete surveillance of human reproductive health and these hormones play pivotal roles in the regulation of gonadal function. New algorithms and data reduction methods will also be developed in conjunction with Core B. This Project will also collaborate with Project 8 in the development of new assay platforms for future development. The current automation of the biomarker assays will increase throughput, decrease costs and simplify standardization. The fifth objective is to apply existing biomarker assays to population-based studies of human reproductive health in other Superfund Projects and will provide this service to Project 2. Taken together this project bridges most of the other projects and cores with a focus on human reproductive health at both the individual and population level.

I. Screen potential environmental hazards studied in other projects for their ability to cause adverse effects on reproductive processes in vitro using primary cultures of human cells.

II. Screen potential environmental hazards studied in other projects for their abilities to cause adverse effects on reproductive processes in vivo using the non-human primate animal model.

III. Adapt all immunoassay biomarkers to the ACS-180 automated platform monitoring the effects of environmental hazards to human reproductive health.

IV. Develop new biomarker assays to evaluate adverse effects of environmental hazards on human reproductive health

V Provide endocrine service for other projects using biomarker assays employed in Specific Aims 1 and 2, possibly new biomarkers from Specific Aim 4 and employ the new platform described in Specific Aim 3.