Integrated transcriptomic and metabolomic analysis reveals the underlying mechanisms for male reproductive toxicity of polystyrene nanoplastics in mouse spermatocyte-derived GC-2spd(ts) cells

BACKGROUND: Polystyrene nanoplastics (PS-NPs), are ubiquitous pollution sources in human environments, posing significant biosafety and health risks. While recent studies, including our own, have illustrated that PS-NPs can breach the blood-testis barrier and impact germ cells, there remains a gap in understanding their effects on specific spermatogenic cells such as spermatocytes. METHODS AND RESULTS: Herein, we employed an integrated approach encompassing phenotype, metabolomics, and transcriptomics analyses to assess the molecular impact of PS-NPs on mouse spermatocyte-derived GC-2spd(ts) cells. Optimal exposure conditions were determined as 24 h with 50 nm PS-NPs at 12.5 μg/mL and 90 nm PS-NPs at 50 μg/mL for subsequent multi-omics analysis. Our findings revealed that PS-NPs significantly influenced proliferation and viability, causing alterations in transcriptome and metabolome profiles. Transcriptomics analysis of GC-2spd(ts) cells exposed to PS-NPs indicated the pivotal involvement of cell proliferation and cycle, autophagy, ferroptosis, and redox reaction pathways in PS-NP-induced effects on the proliferation and viability of GC-2spd(ts) cells. Furthermore, metabolomics analysis identified major changes in amino acid metabolism, cyanoamino acid metabolism, and purine and pyrimidine metabolism following PS-NP exposure. CONCLUSION: Our integrated approach, combining metabolomics and transcriptomics profiles with phenotype data, enhances our understanding of the adverse effects of PS-NPs on germ cells.