Smith, E.M., A.G. McArthur, S. Higgins, N. Kirischian, M. Galus, & J.Y. Wilson. 2010. Hepatic gene expression in zebrafish (Danio rerio) chronically exposed to pharmaceuticals. Presentation at the 31st Annual Meeting of the Society of Environmental Toxicology and Chemistry (North America), Portland, Oregon.Pharmaceuticals are entering the aquatic environment through wastewater effluent yet the biological effects of these compounds are not clear. We have exposed adult zebrafish to acetaminophen, venlafaxine, gemfibrozil, and carbamazepine for 6 weeks at both a low (0.5 μg/L) and high (10 μg/L) dose. The chronic exposure of adult zebrafish to these environmentally relevant pharmaceuticals significantly decreased reproductive output. Liver was collected to analyze gene expression using a microarray approach, from both males and females. Livers were pooled to provide sufficient RNA for microarray and qPCR analyses. Gene expression was determined with a modified Agilent 44K zebrafish microarry using a single channel approach. Significantly different probes were identified with a 2-way ANOVA (sex and treatment) and rank product analyses with a 10% false discovery rate. Acetaminophen exposure resulted in a similar number of probes that were up and down regulated and the differences between low and high dose acetaminophen exposure were small. Venlafaxine exposure produced a more modest change in hepatic gene expression, with the majority of differential gene expression between control and low dose venlafaxine pools. Genes involved in energy metabolism and reproduction or sex hormones were altered with acetaminophen exposure. Cytochrome P450 gene expression was modestly impacted by acetaminophen exposure only. The genes impacted by venlafaxine exposure were also altered with acetaminophen exposure; acetaminophen exposure produced additional gene sets that were up and down regulated in both males and females.
