Comprehensive phenotyping and transcriptome profiling to study nanotoxicity in C. elegans

Engineered nanoparticles are used at an increasing rate in both industry and medicine without fully understanding their impact on health and environment. The nematode Caenorhabditis elegans is a suitable model to study the toxic effects of nanoparticles as it is amenable to comprehensive phenotyping, such as locomotion, growth, neurotoxicity and reproduction. In this study, we systematically evaluated the effects of silver (Ag) and five metal oxide nanoparticles: SiO(2), CeO(2), CuO, Al(2)O(3) and TiO(2). The results showed that Ag and SiO(2) exposures had the most toxic effects on locomotion velocity, growth and reproduction, whereas CeO(2), Al(2)O(3) and CuO exposures were mostly neurotoxic. We further performed RNAseq to compare the gene expression profiles underlying Ag and SiO(2)toxicities. Gene set enrichment analyses revealed that exposures to Ag and SiO(2)consistently downregulated several biological processes (regulations in locomotion, reproductive process and cell growth) and pathways (neuroactive ligand-receptor interaction, wnt and MAPK signaling, etc.), with opposite effects on genes involved in innate immunity. Our results contribute to mechanistic insights into toxicity of Ag and SiO(2) nanoparticles and demonstrated that C. elegans as a valuable model for nanotoxicity assessment.