ENDOCRINE DISRUPTING COMPOUNDS: REPRODUCTIVE , METABOLIC , DEVELOPMENTAL RESPONSES AND MECHANISMS OF ACTION IN SELECTED MODEL ORGANISMS AND CELL LINES

The endocrine-disrupting chemicals (EDCs) have capacity to alter the function of hormonal and homeostatic systems. Issues key to understanding the mechanisms of action of EDC exposure includes the critical windows of susceptibility of target tissues, latency from exposure, mixture effects, dose-response dynamics, and long-term latent effects. Objectives of the proposed project are to study reproductive, metabolic and developmental effects of selected EDCs and mixtures and the mechanism(s) of actions in several model organisms and cell types: (1) Rat Leydig cells: effects and mechanism of action of single and mixed EDCs on steroidogenesis during sexual development; (2) Human HepG2, rat H4IIE and fish ZFL hepatocytes: toxicity, proliferative/apoptotic actions of single EDCs and mixtures; (3) Aquatic organisms: effects of environmentally relevant concentrations of selected EDCs and mixtures on Daphnia magna reproduction and growth of Myriophyllum aquaticum in complex matrices of freshwater ecosystems; (4) Zebrafish: studies on xenobiotic metabolic pathways, with special focus on characterization of ecotoxicologically relevant phase II enzymes. The project is aimed not only to elucidate the effects of environmentally relevant EDCs and mixtures on critical metabolic pathways in mammalian and non-mammalian species, including human cells, but also to strengthen the potential of our research group in fundamental and applied ecophysiological research and in ecological risk assessment.