Photoaged Polystyrene Nanoplastics Result in Transgenerational Reproductive Toxicity Associated with the Methylation of Histone H3K4 and H3K9 in <i>Caenorhabditis elegans</i>

Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants that are ubiquitously detected in various environments and have toxic effects on various organisms. Nevertheless, the transgenerational reproductive toxicity and underlying mechanisms of PS-NPs remain largely unknown, especially for photoaged PS-NPs under ultraviolet irradiation. In this study, only the parental generation (P0) was exposed to virgin and aged PS-NPs at environmentally relevant concentrations (0.1-100 μg/L), and subsequent generations (F1-F4) were cultured under normal conditions. Ultraviolet irradiation induced the generation of environmentally persistent free radicals and reactive oxygen species, which altered the physical and chemical characteristics of PS-NPs. The results of toxicity testing suggested that exposure to aged PS-NPs caused a more severe decrease in brood size, egg ejection rate, number of fertilized eggs, and hatchability than did the virgin PS-NPs in the P0, F1, and F2 generations. Additionally, a single maternal exposure to aged PS-NPs resulted in transgenerational effects on fertility in the F1 and F2 generations. Increased levels of H3K4 and H3K9 methylation were observed in the F1 and F2 generations, which were concomitant with the transgenerational downregulation of the expression of associated genes, such as <i>spr-5</i>, <i>set-17</i>, and <i>met-2</i>. On the basis of correlation analyses, the levels of histone methylation and the expression of these genes were significantly correlated to transgenerational reproductive effects. Further research showed that transgenerational effects on fertility were not observed in <i>spr-5(by134)</i>, <i>met-2(n4256)</i>, and <i>set-17(n5017)</i> mutants. Overall, maternal exposure to aged PS-NPs induced transgenerational reproductive effects via H3K4 and H3K9 methylation, and the <i>spr-5</i>, <i>met-2</i>, and <i>set-17</i> genes were involved in the regulation of transgenerational toxicity. This study provides new insights into the potential risks of photoaging PS-NPs in the environment.