Effects of trilostane and fipronil on the reproductive axis in an early life stage of the Japanese medaka (Oryzias latipes).

Given the critical role of the hypothalamic-pituitary-gonadal (HPG) axis, it is conceivable that perturbations at any point along this axis can potentially affect reproduction in fish and other vertebrates. We investigated the effects of a 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor, trilostane (TRI), and a gamma-aminobutyric acid (GABA)-receptor antagonist, fipronil (FIP), on the HPG axis using an early life stage of the Japanese medaka. The newly hatched larvae were exposed to TRI (100, 300 and 1000 μg/L) and FIP (3, 10 and 30 μg/L), respectively, until 28 days post-hatching. Exposure to TRI decreased the body length in males, whereas FIP inhibited growth in both sexes. The induction of steroidogenesis-regulating genes (including 3β-hsd) in males exposed to TRI, accompanied by increased vtg and er transcription, indicating a compensatory response to the presumed 3β-HSD inhibition. These compensatory responses were not observed in TRI-treated females. Regarding FIP exposure, the GABA blocker resulted in the down-regulation of fshr and lhr. A compensatory up-regulation of steroidogenesis-regulating genes partially explained the elevated transcripts of vtg genes in both males and females after FIP exposure. These results suggest that both the inhibition of 3β-HSD and the antagonism of GABA receptors are relevant modes of endocrine disruption that could impact the normal regulation of the HPG axis.