Toxicogenomic signatures associated with methylmercury induced developmental toxicity in the zebrafish embryos

Methylmercury (MeHg) is a toxicant with adverse effects on embryogenesis from fish to man. The developmental outcomes of MeHg are well understood, but molecular understanding of toxicity is rather limited. We performed here a genome-wide transcriptional analyses of 6, 30, and 50 mu g/L MeHg exposed zebrafish embryos from 4 to 72 h post-fertilization (hpf) using RNA-sequencing and microarray, and conducted a systematical comparison of MeHg-induced transcriptomic responses reported in this and our previous studies. We observed MeHg signifi-cantly to disrupt expression of 1050, 1931, and 2996 genes, respectively including gene ontologies in terms of visual and sensory perception, phototransduction, ferroptosis, and GABAergic synapse. Significantly altered genes were associated with ontology categorized into metabolism, such as fatty acid, amino acid, and glutathione metabolism across all experiments. Expression of genes involved in Wnt, Shh, and Notch signaling pathways previously demonstrated to be crucial for development was changed at varying levels dependent on exposure concentrations and durations. Our findings show MeHg significantly to affect expression of genes associated with tissue and/or organs developmental processing including eye, lateral line, fins, and brain, especially in embryos exposed to 6 mu g/L, which did not cause obviously toxic effects on zebrafish embryos. We obtain 21 genes being significantly altered by MeHg in a concentration and stage independent manner, and might be served as sig-natures for developmental toxicity and/or teratogenic effects.

Automated summary

Methylmercury significantly affected gene expression in zebrafish embryos, particularly the genes involved in visual and sensory perception, phototransduction, ferroptosis, and GABAergic synapse. It also disrupted the expression of genes involved in metabolism, such as fatty acid, amino acid, and glutathione metabolism. Furthermore, genes associated with important developmental signaling pathways like Wnt, Shh, and Notch pathways were also affected. We identified 21 genes that were significantly altered by MeHg independent of concentration and stage, and these genes may serve as signatures for developmental toxicity and/or teratogenic effects.