Mechanisms of developmental toxicity and metabolic disruption in fishes exposed to selenium

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Selenium (Se) is an essential trace element with a narrow margin between required and toxic doses, particularly in fishes. A variety of industrial, agricultural, and municipal practices in Canada and globally result in increased loading of Se into freshwater ecosystems. As a result, many countries, including Canada, are currently revising their regulatory policies for Se to ensure the protection of fish populations. It is well-known that Se is a potent developmental toxicant, causing severe deformities of the eye, cranium, spine, and other anatomical structures in offspring of adult female fish exposed to elevated dietary Se. Recent work by our group has also demonstrated that elevated Se exposure causes disruption of several endocrine systems in fishes that are involved in energy homeostasis, aerobic metabolism, physiological stress, and reproduction. However, the underlying biochemical mechanisms of this endocrine disruption are not clear, and a better understanding of these modes of action will inform regulators that develop water quality policies to protect fish populations and aquatic ecosystem health. The overall goal of this proposed research is to determine mechanisms of developmental toxicity and metabolic disruption arising from Se exposure in fishes. We will use an integrative approach, combining molecular, biochemical, pharmacological, and behavioural techniques to achieve this goal. To test the hypothesis that early life stage developmental toxicities caused by Se arise from oxidative stress (Objective 1), we will use zebrafish embryos exposed to Se in the presence and absence of inducers and inhibitors of antioxidant defenses, followed by determination of gene expression, oxidative stress markers, and deformities in hatched fry. To test the hypothesis that dietary Se exposure in fishes causes an adverse metabolic syndrome that resembles Type II diabetes in humans (Objective 2), we will use zebrafish and rainbow trout to determine effects on key intermediary metabolic processes that regulate energy homeostasis and aerobic metabolism. To test the hypothesis that Se exposure causes impairment of the visual system in fishes (Objective 3), we will use zebrafish to determine expression of key genes involved in eye development, histopathology of eye structures, and functional responses via several behavioural assays that provide evidence of a fully functional visual system. Overall, these innovative, integrated experiments will increase our mechanistic understanding of the toxicological responses associated with environmentally relevant Se exposures, which may be applicable to other classes of aquatic contaminants that display a common etiology. The objectives of this research proposal fit closely with my long-term research goal, which is to investigate mechanisms of developmental and reproductive toxicities in fishes exposed to priority aquatic pollutants.