Activation of FGF signal in germline mediates transgenerational toxicity of polystyrene nanoparticles at predicted environmental concentrations in Caenorhabditis elegans

Nanoplastics in the environment could cause the ecological and health risks. Recently, the transgenerational toxicity of nanoplastic has been observed in different animal models. In this study, using Caenorhabditis elegans as an animal model, we aimed to examine the role of alteration in germline fibroblast growth factor (FGF) signal in mediating the transgenerational toxicity of polystyrene nanoparticle (PS-NP). Exposure to 1-100 μg/L PS-NP (20 nm) induced transgenerational increase in expressions of germline FGF ligand/EGL-17 and LRP-1 governing FGF secretion. Germline RNAi of egl-17 and lrp-1 resulted in resistance to transgenerational PS-NP toxicity, indicating the requirement of FGF ligand activation and secretion in formation of transgenerational PS-NP toxicity. Germline overexpression of EGL-17 increased expression of FGF receptor/EGL-15 in the offspring, and RNAi of egl-15 at F1 generation (F1-G) inhibited transgenerational toxicity of PS-NP exposed animals overexpressing germline EGL-17. EGL-15 functions in both the intestine and the neurons to control transgenerational PS-NP toxicity. Intestinal EGL-15 acted upstream of DAF-16 and BAR-1, and neuronal EGL-15 functioned upstream of MPK-1 to control PS-NP toxicity. Our results suggested the important role of activation in germline FGF signal in mediating the induction of transgenerational toxicity in organisms exposed to nanoplastics in the range of μg/L.