Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and...

Age/stage sensitivity is considered a significant factor in toxicity assessments. Previous studies investigated cadmium (Cd) toxicosis in Caenorhabditis elegans, and a plethora of metal-responsive genes/proteins have been identified and characterized in fine detail; however, most of these studies neglected age sensitivity and stage-specific response to toxicants at the molecular level. This present study compared the transcriptome response between C. elegans L3 vs L4 larvae exposed to 20 µM Cd to explore the transcriptional hallmarks of stage sensitivity. The results showed that the transcriptome of the L3 stage, despite being exposed to Cd for a shorter period, was more affected than the L4 stage, as demonstrated by differences in transcriptional changes and magnitude of induction. Additionally, T08G5.1, a hitherto uncharacterized gene located upstream of metallothionein (mtl-2), was transcriptionally hyperresponsive to Cd exposure. Deletion of one or both metallothioneins (mtl-1 and/or mtl-2) increased T08G5.1 expression, suggesting that its expression is linked to the loss of metallothionein. The generation of an extrachromosomal transgene (PT08G5.1:: GFP) revealed that T08G5.1 is constitutively expressed in the head neurons and induced in gut cells upon Cd exposure, not unlike mtl-1 and mtl-2. The low abundance of cysteine residues in T08G5.1 suggests, however, that it may not be involved directly in Cd sequestration to limit its toxicity like metallothionein, but might be associated with a parallel pathway, possibly an oxidative stress response.