Responses of the medaka HPG axis PCR array and reproduction to prochloraz and ketoconazole

Effects of two model imidazole-type fungicides, prochloraz (PCZ) and ketoconazole (KTC), on the hypothalamic-pituitary-gonadal (HPG) axis of the Japanese medaka (Oryzias latipe) were examined by use of real time PCR (RT-PCR) array. Fourteen-week-old Japanese medaka were exposed for seven days to concentrations of PCZ or KTC from 3.0 to 300 mu g/L. Exposure to KTC or PCZ caused significant reduction of fecundity of Japanese medaka and down-regulated expression of estrogen receptor (ER)-alpha and egg precursors in livers of males and females. However, PCZ was more potent than KTC both in modulating transcription and causing lesser fecundity. Exposure to nominal 30 mu g PCZ/L resulted in 50% less fecundity and significant down-regulation of vitellogenin II expression, but KTC did not cause such effects at this concentration. Exposure to PCZ caused a compensatory up-regulation in cytochrome P450 c17 alpha hydroxylase, 17,20-lyase (CYP17) and aromatase (CYP19) expression in the ovary, while KTC did not. Furthermore, the ecologically relevant end point, fecundity was log-log related to mRNA level of six genes in livers of females.