The role of the aryl hydrocarbon receptor in persistent effects of toxicants in fish

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The common environmental contaminants, dioxins and petroleum hydrocarbons, kill very young fish mainly by causing severe defects in the heart and blood vessels. These pollutants work by changing gene expression at important points while the heart is developing, but the identity of all the genes involved is still unclear. Recent work from this laboratory suggests that exposure to even low levels of these contaminants (lower than what is needed to kill young fish) hampers fish health. Specifically, we have found that a very brief exposure during development affects how well exposed fish swim in adulthood and leads to excess fattiness. From our previous work, it is unclear if enough of the pollutant simply stays in the bodies of the fish until adulthood to cause these persistent effects. Another possibility is that the heart and blood vessel defects cause poor blood circulation, leading to poor muscle strength and poor removal of fat from fatty tissues. The final possibility is that something is changing how genes are being allowed to make proteins. Recent advances in our understanding of molecular biology show that DNA in most organisms possesses mechanisms where certain genes can be silenced or enhanced through so-called 'epigenetic mechanisms'. Thus, the major goal of this proposal is to determine the lowest level of pollutant needed to cause persistent effects in fish. We also want to identify important proteins that produce the pollutant effects and whether epigenetic mechanisms are responsible. The proposed experiments will assess cardiovascular structure and function using high resolution micro-ultrasound, 3-D image analysis software with confocal microscopy, and advanced molecular techniques (transgenic fish with green fluorescent vasculature, qPCR and knock down techniques) in zebrafish (Danio rerio). Our goal is to show that these pollutants affect the critically important ability of fish to swim after a single exposure if that exposure occurs when they are very young. This information will allow the government to change environmental regulations to better protect wild fish populations in Canada and elsewhere.