Analysis of Transcriptional Response in Zebrafish Eleutheroembryos Exposed to Climbazole: Signaling Pathways and Potential Biomarkers

摘要

Climbazole is an antifungal active ingredient used in personal care products. After application this chemical reaches the aquatic environment and may pose a risk to fish. In the present study, we measured the transcriptional effects of essential genes related to a wide range of signaling pathways on zebrafish eleutheroembryos exposed to climbazole at environmentally relevant and predicted worst-case environmental concentrations, and explored the potential biomarkers via partial least squares discriminant analysis. Transcription analysis covering up to 73 genes revealed significant down-regulation of circadian rhythm- and steroidogenesis-related genes in zebrafish embryos and larvae after exposure to environmentally relevant concentrations of climbazole. This topical antifungal agent also modulated the transcripts of genes involved in inflammation, oxidative stress, oocyte maturation, and sexual differentiation at predicted worst-case environmental concentrations. In addition, mpr alpha, igf3, nr1d1, nr1d2b, cyp19a1a, vtg1, il-1 beta, and il-8 were chosen as potential biomarkers in embryonic zebrafish following exposure to climbazole. These findings can help us understand the remarkable transcriptional response to climbazole in the early life stage of zebrafish. Future research should elucidate whether the transcriptional modulation translates into metabolic phenotypes associated with the corresponding signaling pathways. Environ Toxicol Chem 2019;38:794-805. (c) 2019 SETAC