Fipronil-induced toxic effects in zebrafish (Danio rerio) larvae by using digital gene expression profiling

Fipronil residue has caused widespread concern around the world, especially after the recent "toxic eggs" event in seven European countries. To evaluate the effects of fipronil on vertebrates, zebrafish larvae were used as an animal model to examine the lethal effect, developmental phenotypes at high doses, and possible mechanisms of toxicity by employing digital gene expression (DGE) profiling at environmentally relevant doses. The results of acute toxicity test indicated that treatment with fipronil from 75 h post-fertilization (hpf) led to the death of larvae with a 96-h LC50 value of 459 μg/L, as well as abnormal development including bent spine and shortened body length. Besides, we obtained high-quality-sequencing DGE profilings at fipronil concentrations of 0.5, 5, and 50 μg/L, respectively. The results revealed that 44 differentially expressed genes, 10 GO terms, and 3 KEGG pathways were overlapped among the three concentrations. MIDN, one of the 44 differentially expressed genes, showed dose-dependent responses at the transcriptional level, indicating that it was possibly a potential biomarker to reflect fipronil toxicity in zebrafish. Furthermore, we presumed that the changing transcriptional level of AP-1 family was possibly a reason for bent spine and shortened body length in larvae exposed to fipronil. Concurrently, altered abundance of transcripts of the ELOVL family in a key step of fatty acid elongation could possibly lead to the accumulation of long-chain fatty acids. Collectively, our results suggested that exposure to fipronil caused lethal and developmental toxicity in zebrafish larvae, and demonstrated the need for a comprehensive understanding of the potential mechanisms of fipronil toxicity due to fipronil's frequent presence in the environment and its potential threat to human health.