The exposure and subsequent accumulation of cadmium within biological systems triggers destructive outcomes, as it inhibits or displaces essential metals such as Zn. Cadmium induces the synthesis of metallothioneins (MTs) and antioxidant proteins that are involved in neutralizing the toxicity. Despite the activation of detoxification mechanisms, cadmium has the potential to exert long-lasting direct/indirect consequences of exposure that might also affect the (unexposed) next generation(s).
Caenorhabditis elegans is a well-established eukaryotic organism model that was chosen for this study to define, by means of the RNAseq, the transcriptomic fingerprints of the cadmium exposome. In addition, the accumulation and the distribution of cadmium were determined by means of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to identify the outcome of the exposure in parents and the resultant progeny. In summary, this study highlighted that
C. elegans has two MTs genes, both capable of binding metals. The deletion of a single MT reduced significantly the accumulation of Cd, the deletion of
mtl-1, however, suppressed metal accumulation more than the deletion of
mtl-2, which might indicate
mtl-1’s importance in metal metabolism. In addition,
T08G5.1, a hitherto uncharacterized transcript located upstream of
mtl-2, was shown to be hypersensitive to cadmium exposure. The deletion of one or both MTs substantially increased the expression of
T08G5.1 in mutant strains which suggests that
T08G5.1 expression is linked to the loss of MTs. The generation of an extrachromosomal transgene (
PT08G5.1::GFP) revealed a constitutive expression in the head neurons and an expression that was metal inducible in gut cells, not unlike
mtl-1 and
mtl-2. The low abundance of cysteine residues in
T08G5.1 suggests that it is not directly involved in the binding of cadmium but may possibly form part of the oxidative stress response. Although metals were not shown to be transferred from exposed parents to the (unexposed) progeny, the expression of certain genes (e.g.,
mtl-1,
T22F3.11, and
C17F4.3) was elevated for at least two generations, suggesting their possible involvement in the transmission of transgenerational effects within the context of metal stress. To conclude, cadmium toxicity is not limited to the expression of MTs, other (uncharacterized) players are also involved. Their characterization is called for to allow the fine mechanistic details of the cadmium exposome to be unravelled.