INVESTIGATING IMPACTS OF ACUTE AND CHRONIC EXPOSURE TO ENDOCRINE DISRUPTING COMPOUNDS ON THE REPRODUCTIVE AND STRESS-RESPONSIVE AXES OF ZEBRAFISH (DANIO RERIO)
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Regulatory agencies aim to keep us safe from harmful chemical exposures by placing limits on levels of toxic compounds in our environment, food, consumer products, and more. However, these limits are set based on exposure levels where broad adverse effects are no longer observed. Additionally, these limits are usually set at much higher concentrations than those at which hormones work to control many critical biological functions. Endocrine disrupting compounds (EDCs), which can mimic or interfere with these functions, can act below the suggested safe levels and lead to adverse health effects. Therefore, exposure studies are needed to better understand the potential harmful effects of EDCs. The overall purpose of this dissertation research was to understand EDC exposure effects on the reproductive hypothalamic-pituitary-gonadal (HPG) and the stress responsive hypothalamic-pituitary-adrenal (HPA) hormonal axes. I studied the exposure effects of bisphenols and cadmium, common environmental and food contaminants, on zebrafish development, gene expression, hormone production, and behavior. To model environmental exposures, these investigations included environmentally relevant concentrations and mixtures. An acute bisphenol study was used to determine if exposure to a mixture of bisphenols augments effects of individual bisphenol exposures. The chronic bisphenol mixture exposure study investigated exposure effects on both reproductive and stress-related endpoints across multiple generations. An acute cadmium exposure was also conducted to understand the effects of early developmental exposure on the stress response. Acute exposure to individual bisphenols led to changes in reproductive gene expression at environmentally relevant concentrations. Additive or synergistic effects of the mixture exposure were only seen in the highest concentration. In the acute cadmium exposure, however, environmentally relevant concentrations, did not lead to any changes in stress response. The environmentally relevant concentration in chronic bisphenol exposure impacted stress-related behavior in the F0 generation, and the highest concentration led to fertility deficits and stress axis dysregulation. Changes in both behavior and gene expression were seen in subsequent generations of offspring of fish exposed to environmentally relevant concentrations. Taken together, environmentally relevant exposures are still a concern, although the effects may not always be seen in the directly exposed group but may be seen in offspring.
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Schaffer, Chris