Transcriptome reveals overview of Ca²⁺ dose-dependent metabolism disorders in zebrafish larvae after Cd²⁺ exposure

Cadmium (Cd), a ubiquitous environmental hazardous heavy metal, poses a significant threat to the health of aquatic organisms, including teleosts. Although the toxic profile of Cd is well recognized, little is known regarding the overall view of toxic responses to varying aquatic environmental parameters (e.g., water hardness) at an individual level. Herein, differences in water hardness were partially mimicked by adjusting Ca²⁺ levels in E3 medium. As an in vivo model, zebrafish embryos were exposed to variable Ca²⁺ levels (NV, normal Ca²⁺; LV, low Ca²⁺; HV, high Ca²⁺) alone or combined with 30.7 µg/L Cd²⁺ (NC, LC, and HC, respectively) until 144 hr post-fertilization. The genome-wide transcriptome revealed differentially expressed genes between groups. Functional enrichment analysis found that biological processes related to metabolism, particularly lipid metabolism, were significantly disrupted in NC and LC treatments, while a remission was observed in the HC group. Biochemical assays confirmed that the decrease in Ca²⁺ enhanced synthesis, inhibited mobilization and increased the storage of lipids in Cd²⁺ treatments. This study suggests that the toxic effect of Cd on biological pathways will be influenced by Ca²⁺, which will improve the toxicological understanding and facilitate accurate assessment of Cd.