Alteration in Wnt signaling mediates induction of transgenerational toxicity of polystyrene nanoplastics in C. elegans.

Polystyrene nanoparticles (PS-NPs) have a potential toxicity on offspring after the exposure. However, the molecular basis for PS-NP in inducing transgenerational toxicity remains largely unknown. In this study, the role and the underlying mechanism of germline Wnt signaling in regulating transgenerational toxicity of PS-NPs were determined using an in vivo animal model of Caenorhabditis elegans. Exposure to PS-NP (1-100 μg/L) increased expression of Wnt ligand LIN-44 and decreased expression of Wnt receptor MIG-1. After the exposure, the transgenerational PS-NP toxicity on locomotion behavior and brood size were inhibited in lin-44(RNAi) nematodes, while enhanced in mig-1(RNAi) nematodes. The resistance to transgenerational PS-NP toxicity induced by RNAi of lin-44 in P0 generation (P0-G) was inhibited by RNAi of mig-1 in F1-G. In addition, after PS-NP exposure, germline RNAi of lin-44 at P0-G could increase the mig-1 expression in F1-G. Exposure to PS-NP (1-100 μg/L) further decreased expressions of Dishevelled proteins of DSH-1/2, increased APC complex component APR-1, and decreased expression of BAR-1/β-catenin. Meanwhile, transgenerational PS-NP toxicity was enhanced by RNAi of dsh-1, dsh-2, or bar-1 and inhibited by RNAi of apr-1, suggesting that the DSH-1/2-APR-1-BAR-1 signaling cascade acted downstream of Wnt receptor MIG-1 to control transgenerational PS-NP toxicity. Moreover, BAR-1 acted upstream of DVE-1 to activate mitochondrial unfolded protein response (mt UPR) against the transgenerational PS-NP toxicity. Our data highlights the potential link between alteration in germline Wnt signaling and induction of transgenerational nanoplastic toxicity in organisms.