Effect of gestodene on the reproduction of zebrafish (Danio rerio)

Gestodene is a synthetic progestin and a potent human progesterone receptor (PR) agonist, used in contraceptives and hormone therapy. However, in vitro data suggest that gestodene acts as a PR antagonist in zebrafish (Danio rerio). In the present study, adult zebrafish of both sexes were exposed to gestodene at concentrations of 100 and 600 ng∙L^-1 for 45 days. The effect of gestodene on cumulative oviposition was monitored throughout the experiment. Exposure to 600 ng∙L^-1 of gestodene reduced cumulative oviposition per female compared to the control. Histological analysis showed no major histopathological alterations, except for a lower number of spermatocytes observed in the group exposed to 100 ng∙L^-1. Hormone analysis revealed a lower plasma level of 11-ketotestosterone in males exposed to 600 ng∙L^-1. Furthermore, gestodene exposure altered mRNA expression of genes involved in the hypothalamus-pituitary-gonad and hypothalamus-pituitary-thyroid axes in the brain-pituitary complex, gonads, and liver of exposed fish.