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

Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after 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 , and nhr-47 expressions were increased and nhr-12 expression 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 of daf-12 , nhr-14 , and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3 , daf-28 , and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes ( daf-2 , vab-1 , and/or mig-1 ), were dysregulated by the RNAi of daf-12 , nhr-14 , nhr-47 , and nhr-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.