Transgenerational Response of Germline Nuclear Hormone Receptor Genes to Nanoplastics at Predicted Environmental Doses in Caenorhabditis elegans

Transgenerational nanoplastic toxicity could be detected inCaenorhabditis elegansafter exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes,daf-12,nhr-14, andnhr-47expressions were increased andnhr-12expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi ofdaf-12,nhr-14, andnhr-47caused resistance, whereas RNAi ofnhr-12conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions ofins-3,daf-28, andins-39encoding insulin ligands,efn-3encoding Ephrin ligand, andlin-44encoding Wnt ligand, as well as expressions of their receptor genes (daf-2,vab-1, and/ormig-1), were dysregulated by the RNAi ofdaf-12,nhr-14,nhr-47, andnhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.