Nanoplastics cause transgenerational toxicity through inhibiting germline microRNA mir-38 in C. elegans

Nanoplastic exposure potentially caused the induction of transgenerational toxicity. Nevertheless, the molecular basis for nanoplastic exposure-induced transgenerational toxicity remains largely unclear. Using Caenorhabditis elegans as an animal model, we examined the role of germline microRNA (miRNA) mir-38 in regulating the transgenerational toxicity of polystyrene nanoparticles (PS-NPs). After the exposure, 1-100 μg/L PS-NP decreased expression of germline mir-38. Meanwhile, germline mir-38 overexpression conferred a resistance to transgenerational PS-NP toxicity, which suggested that the decrease in germline mir-38 mediated the induction of transgenerational PS-NP toxicity. In the germline, mir-38 regulated transgenerational PS-NP toxicity by inhibiting activity of downstream targets (NDK-1, NHL-2, and WRT-3). Among these three downstream targets, germline NDK-1 further controlled transgenerational PS-NP toxicity by suppressing the function of KSR-1/2, two kinase suppressors of Ras. Therefore, in the germline, the decrease in mir-38 mediated induction of transgenerational PS-NP toxicity by at least inhibiting signaling cascade of NDK-1-KSR-1/2 in nematodes. The findings in this study are helpful for providing relevantly molecular endpoints to assess potential transgenerational toxicity of nanoplastics.