背景:聚苯乙烯纳米塑料(PS-NP),是人类环境中普遍存在的污染源,构成重大的生物安全和健康风险。虽然最近的研究,包括我们自己的,已经说明PS-NP可以突破血液睾丸屏障并影响生殖细胞,在理解它们对特定生精细胞如精母细胞的影响方面仍存在差距。
结果:这里,我们采用了包含表型的综合方法,代谢组学,和转录组学分析,以评估PS-NP对小鼠精母细胞衍生的GC-2spd(ts)细胞的分子影响。最佳暴露条件确定为24小时,其中50纳米PS-NP为12.5μg/mL,90纳米PS-NP为50μg/mL,用于随后的多组学分析。我们的研究结果表明,PS-NP显著影响增殖和活力,导致转录组和代谢组的变化。暴露于PS-NP的GC-2spd(ts)细胞的转录组学分析表明细胞增殖和周期的关键参与,自噬,铁性凋亡,PS-NP诱导的GC-2spd(ts)细胞增殖和活力的氧化还原反应途径。此外,代谢组学分析确定了氨基酸代谢的主要变化,氰基氨基酸代谢,PS-NP暴露后嘌呤和嘧啶代谢。
结论:我们的综合方法,将代谢组学和转录组学概况与表型数据相结合,增强了我们对PS-NP对生殖细胞的不利影响的理解。
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.
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.
CONCLUSIONS: Our integrated approach, combining metabolomics and transcriptomics profiles with phenotype data, enhances our understanding of the adverse effects of PS-NPs on germ cells.