Long-term nanoplastics exposure results in multi and trans-generational reproduction decline associated with germline toxicity and epigenetic regulation in Caenorhabditis elegans

The environmental risk from long-term plastic pollution is growing. We investigated the multi and trans-generational reproductive toxicity of nanoplastics (NPs) in Caenorhabditis elegans and the underlying mechanisms over five generations. Following a single maternal exposure (F0) to NPs (100 nm; 1, 10, 50, or 100 mg/L) for 72 h, the subsequent generations (F1-F4) were cultured under NPs-free conditions. We showed that the total brood size was significantly reduced across all offspring generations (F1-F4). NPs accumulated in the intestine of C. elegans in the F0 generation, but not in the germline system, and not observed in subsequent generations. Chromosomal aberrations in oocytes and germline cell apoptosis were significantly elevated in the NPs-exposed F0 generation and in subsequent unexposed generations. Likewise, the expression of ced-3 was increased across generations, regulated by hypomethylation in the promoter region of ced-3 after maternal NPs exposure. Finally, NPs exposure reduced the expression of epigenesis-related genes met-2, set-2, and spr-5 and the trans-generational effects of maternal NPs exposure were not observed in met-2, set-2, and spr-5 RNAi worms. We demonstrate that a single long-term maternal NPs exposure can cause multi and trans-generational reproduction decline in C. elegans, which may be associated with germline toxicity and epigenetic regulation.