Multi-omics analysis of testis after long-term exposure to polystyrene nanoplastics reveals premature testicular aging and age-dependent damage in mice.

BACKGROUND

Nanoplastics (NPs) are emerging contaminants posing significant risks to human health due to their enhanced cellular penetration. NPs have been shown to damage human testes and epididymides, impairing male fertility. However, the specific testicular damage and underlying mechanisms induced by NPs at different ages have not been thoroughly investigated.

RESULTS

In this study, we exposed young (3-month-old) and old (17-month-old) male mice to long-term (3 months) polystyrene nanoplastics (PS-NPs). The results showed that PS-NPs extensively disrupted testicular structures and functions in both age groups, leading to excessive germ cell loss, tubular degeneration, fibrosis, and declined sperm quality. Young mice exhibited premature testicular aging, while old mice showed more severe testicular damage, indicating age-dependent injury. Mechanistically, proteomics combined with Gene Ontology analysis revealed that PS-NPs primarily disturbed RNA metabolism in young mice, whereas DNA catabolism, collagen, and extracellular matrix metabolism were extensively impaired in old mice. Additionally, integrated proteomic and metabolomic analyses, along with assays conducted on primary Leydig cells, suggested that PS-NPs downregulated scavenger receptor class B type I (SR-BI), consequently impeding testosterone synthesis and aggravating testicular aging in young mice.

CONCLUSIONS

Integrated with multi-omics analyses, our study collectively extends the current understanding of PS-NP-induced testicular and sperm toxicology, highlighting age- and duration-dependent risks to male reproduction. Protecting mRNA metabolism and testosterone production may help preserve reproductive capacity in young males exposed to NPs.