Impact/Purpose:

The objective of this project is to determine whether exposure to environmental agents, during certain key periods of development, will increase the risk of specific anomalies of the reproductive system. The protocols that will be used in these studies will facilitate our understanding of the range of doses necessary to produce the adverse change and whether treatment during certain sensitive periods of development results in doses that are at or below those known to alter reproductive function in adulthood and whether or not they are in the range of human environmental exposures. As we understand very little about the extent to which anomalies in the rat reflect the potential for similar adverse changes in the human, the integrated approach offered in this proposal will provide insight into the extent to which these processes may occur in similarly exposed human populations.

Description:

The primary hypothesis to be tested in this series of studies is whether or not exposure to environmental agents, during certain key periods of development, will increase the risk of specific anomalies of the reproductive system. Embedded in this hypothesis is the assumption that some environmental agents can disrupt normal brain-pituitary-gonadal development to the extent that reproductive organs will display an increased risk of inflammation, dysplasia and tumor formation. These studies will provide an opportunity to determine the mode of action through which these changes are induced, identify the specific mechanisms involved when the developing neuroendocrine system is perturbed, map the potential involvement of any associated changes in immune function that may occur concomitantly and describe the specific lesions that occur in the brain, pituitary and reproductive tissues. The protocols that will be used in these studies will facilitate our understanding of the range of doses necessary to produce the adverse change and whether treatment during certain sensitive periods of development results in doses that are at or below those known to alter reproductive function in adulthood and whether or not they are in the range of human environmental exposures. The first series of studies will investigate endocrine disrupting chemicals (EDCs) that alter prolactin status, which may result in changes in reproductive and immune finction. The final set of studies will investigate the effect of EDCs on mammary gland development and tumorogenesis are described. Both sets of studies will be carried out with the goal of developing a rodent model for use in future testing and studying human disease status.

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