The Effects of Parental Carbamazepine and Gemfibrozil Exposure on Sexual Differentiation in Zebrafish (Danio rerio)

Abstract

Endocrine-disrupting compounds (EDCs) interfere with the physiology of hormone systems. Traditionally, steroidogenic pharmaceuticals have been studied as EDCs however there has been growing evidence that non-steroidogenic pharmaceuticals can alter sex steroid levels and impair reproductive functions in fish. This is of concern as pharmaceuticals are detected in surface waters at the ng L-1 to µg L-1 range. Zebrafish (Danio rerio) were exposed to 10 µg L-1 of the pharmaceuticals carbamazepine and gemfibrozil for 6 weeks. Male-biased sex ratios were observed in the sexually mature offspring after paternal exposure, suggesting that sexual differentiation may be impacted in juveniles. Currently, the ability of pharmaceuticals to interfere with sexual differentiation of parentally exposed offspring is unknown. This thesis examined the gonad histology of juvenile zebrafish to understand how sexual differentiation was affected in the offspring of exposed parents. Paternal, but not maternal, exposure to carbamazepine resulted in a significantly faster sexual differentiation of the gonads and led to a male-biased sex ratio; these effects were not observed when both parents were exposed. Combined paternal and maternal exposure to gemfibrozil resulted in significantly faster sexual differentiation and paternal, but not maternal, exposure to gemfibrozil led to male-biased sex ratios. Interestingly, sex ratios observed in the juveniles did not always reflect those found in the same lineage at sexual maturity, suggesting a sex reversal, including a male to female transition, occurred past the juvenile sexual differentiation period in some fish. This thesis demonstrates that pharmaceuticals have the ability to disrupt sexual differentiation in the F1 offspring of exposed parents and that paternal exposure is most relevant for offspring effects.