Nanoplastic at environmentally relevant concentrations induces toxicity across multiple generations associated with inhibition in germline G protein-coupled receptor CED-1 in Caenorhabditis elegans

Nanoplastics at environmentally relevant concentrations (ERCs) could cause transgenerational toxicity on organisms. Caenorhabditis elegans is an important model for the study of transgenerational toxicology of pollutants. Nevertheless, the underlying mechanisms for the control of transgenerational nanoplastic toxicity by germline signals remain largely unclear. In C. elegans, exposure to 1-100 μg/L polystyrene nanoparticle (PS-NP) decreased expression of germline ced-1 encoding a G protein-coupled receptor at parental generation (P0-G). After PS-NP exposure at P0-G, transgenerational decrease in germline ced-1 expression could be detected. Meanwhile, the susceptibility to transgenerational PS-NP toxicity was observed in ced-1(RNAi) animals. After PS-NP exposure at P0-G, germline RNAi of ced-1 increased expressions of met-2 and set-6 encoding histone methylation transferases. The susceptibility of ced-1(RNAi) to transgenerational PS-NP toxicity could be inhibited by RNAi of met-2 and set-6. Moreover, in PS-NP exposed met-2(RNAi) and set-6(RNAi) nematodes, expressions of ins-39, wrt-3, and/or efn-3 encoding secreted ligands were decreased. Therefore, our results demonstrated that inhibition in germline CED-1 mediated the toxicity induction of nanoplastics at ERCs across multiple generations in nematodes.