Persistent effects of early-life arsenic exposure in Caenorhabditis elegans

Arsenic exposure is a major global health challenge. In addition to well-documented toxic effects in exposed people and animals, there is evidence that exposure to arsenic may lead to transgenerational effects. Transgenerational effects of low levels of exposure are challenging to study in species with long generation times. The model organism Caenorhabditis elegans offers the ability to quickly carry out transgenerational experiments with very large sample sizes of isogenic animals, reducing variation, and numerous biological replicates, to increase statistical rigor. An important challenge historically associated with this species for such work is uncertainty about internal dosimetry and toxicokinetics. Here, we report a 4-generation experiment in which C. elegans were exposed during larval development to sodium arsenite concentrations in the parental generation at concentrations resulting in no or mild growth inhibition up to significant growth inhibition. These exposures resulted in internal concentrations between 0.4 and 6.7 nM and rapid excretion (t_1/2 = 3 hours), despite the lack of arsenic methylation in this species. These exposures had strong and significant effects on the exposed generation later in life, but no transgenerational effects were detected. We discuss possible reasons for this "negative" result. We also report strong similarity of the nematode transcriptomic, metabolomic, and fat accumulation responses in the exposed generation to responses reported in other organisms, including persistent alterations in cysteine and fatty acid metabolism, phase II and III metabolic processes, and increased adiposity. Finally, we discuss ways to take advantage of this species difference in arsenic metabolism for the use of C. elegans in toxicology testing.