Pathway-based approaches in ecotoxicological research: Evaluation of complex mixtures on fathead minnow reproduction and development

University of Minnesota M.S. thesis.July 2015. Major: Integrated Biosciences. Advisor: Gerald Ankley. 1 computer file (PDF); viii, 108 pages.Mixtures of natural and synthetic compounds are ubiquitously detected in wastewater treatment plant (WWTP) effluents and surrounding surface waters. Of particular concern are endocrine-disrupting compounds that can affect hypothalamic-pituitary-gonadal axis function in exposed organisms. Reproductive effects of exposure to a historically estrogenic WWTP effluent were examined in a 21-d real-time exposure using fathead minnows. Molecular and biochemical endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment were examined. Analytical chemistry results were used to construct a chemical-gene interaction network to aid in targeted gene expression analyses. Estrone was consistently detected in the effluent and was subsequently used in an exposure aimed to implement whole-mount in situ hybridization with fathead minnow embryos to examine developmental effects at early-life stages. The results provide insights into the significance of pathway-based effects with regard to predicting adverse reproductive and developmental outcomes