CARBAMAZEPINE & GEMFIBROZIL AFFECT ZEBRAFISH REPRODUCTION

Abstract

Pharmaceuticals are emerging surface water contaminants, and are manufactured, used, and released into environment in considerable amounts. Concerns have been raised due to the inherent potency and bioactivity of these molecules, which makes effects at low concentrations more likely. The ubiquitous presence and stability of pharmaceuticals brings up concerns about the frequency and length of exposures. However, the distribution and fate of these compounds in surface water bodies is not clear. There is limited information about the potential effects in non-target, especially aquatic, species vulnerable to cumulative or lifelong exposures. Carbamazepine (CBZ) and gemfibrozil (GEM) are two of the most frequently detected pharmaceuticals in surface water. This thesis examined sub-lethal adverse reproductive effects of chronic direct exposure of CBZ and GEM to F0 zebrafish and several generations of unexposed offspring; the effects of exposure on testicular steroidogenesis were also examined. Chronic exposure of zebrafish to CBZ and GEM reduced ex vivo production of 11KT in testes. In vivo, CBZ decreased reproductive output, 11-ketotestosterone (11KT), male courtship and aggression behaviours, and sperm morphology in F0 parents. The F1, F2 and F3 offspring of CBZ exposed males had lower reproductive output, altered courtship, aggression, sperm morphology and lower 11KT compared to fish from the unexposed lineage. The adverse effects persisted into the F3 generation which suggested transgenerational paternal effects. GEM decreased reproductive output in F0 parents and a reduction in 11KT, altered male courtship, aggression and sperm morphology. Unexposed F1 male offspring, but not other generations, had sub-lethal toxic effects from parental exposure. We therefore suggest that CBZ and GEM act as endocrine disruptors in fish and that chronic exposure may reduce male reproductive fitness.