Chronic Exposure to Environmentally Relevant Pharmaceutical Concentrations Effects Reproductive and Developmental Physiology in Zebrafsih (Danio rerio)

Abstract

The presence of pharmaceuticals and personal care products (PPCPs) in the aquatic environment has been a growing issue of concern over the past twenty years. Compounds from various pharmaceutical classes have been detected at ng to µg L-1 concentrations in waste water effluent, surface, ground and drinking water. Although the concentrations required for these compounds to elicit a therapeutic response is higher than what is detected in the aquatic environment, the impacts pharmaceuticals may have on aquatic species under chronic or mixture conditions remains largely unknown. This thesis addresses this knowledge gap by evaluating the impacts of chronic exposure to four frequently detected pharmaceuticals and pharmaceutical mixtures on the physiology of the model teleost, zebrafish (Danio rerio). Environmentally relevant concentrations of acetaminophen, carbamazepine, gemfibrozil and venlafaxine significantly reduced zebrafish fecundity and increased embryonic mortality. Pharmaceutical exposure to gemfibrozil and carbamazepine altered the structural morphology of the ovary; all compounds tested altered kidney histology. As exposure in the environment is rarely ever to a single compound, animals were exposed to a quaternary mixture of the four compounds and wastewater effluent. Under mixture conditions, reproductive, developmental and histological effects were also observed, however they generally were more severe then those seen with single compound exposure. Overall, these results showed that chronic, low dose pharmaceutical exposure were sufficient to induce a suite of physiological effects suggesting an overall decrease in fish health. Effects on offspring after chronic parental exposure to gemfibrozil and carbamazepine resulted in alterations in male breeding behaviour, reduced fecundity, decreased sperm velocity and induced morphological changes to spermatozoa. These novel findings expand the limited knowledge base of studies examining effects on offspring. Lastly, acetaminophen was confirmed to elicit its developmental impacts in fish via the cyclooxygenase pathway; the same mechanism of action as observed in mammals. This thesis has made significant contributions to identifying the physiological consequences of environmental pharmaceutical toxicity to fish.