Progestins and Antiprogestins Affect Gene Expression in Early Development in Zebrafish (Danio rerio) at Environmental Concentrations

Progesterone (P4) and synthetic progestins (gestagens) from contraceptives and hormone therapy occur in treated wastewater and surface water, and they may have adverse effects on aquatic organisms. Little is known about the molecular and reproductive effects of P4 and synthetic progestins in fish, and effects of the antiprogestin mifepristone (RU486, an abortive) are unknown. We aimed at elucidating effects on the hormone system by quantitative determination of transcriptional changes of target genes induced by 2, 20, and 200 ng/L P4, RU486, norethindrone (NET), and levonorgestrel (LNG). We exposed zebrafish embryos for 144 h post fertilization (hpf) to these compounds and analyzed expressional changes of ar, esr1, vtg1, hsd17 beta 3, and progesterone (pgr), mineralo- (mr), and glucocorticoid (gr) receptors, each at 48, 96, and 144 hpf Concentrations of NET and LNG were constant during exposure, while P4 and RU486 decreased. P4 and RU486 were the most potent steroids. Significant up to 4-fold induction of pgr, ar, mr, and hsd17b3 occurred at 2 ng/L P4 and higher, while RU484 inhibited pgr expression. NET and LNG modulated some transcripts mainly above 2 ng/L. The expressional chances occurring at environmental levels may translate to negative interference with differentiation of brain and gonads, and consequently reproduction.