Ma Sheng, Li Sisi, Jiang Shengyao, Wang Lirui, Zhan Dian, Xiong Manyi, Jiang Yanping, Huang Qixian, Kui Haozhan, Li Xinhong
School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200241, China.
Shanghai Key Laboratory for Veterinary and Biotechnology, Shanghai 200241, China.
ACS Nano. 2025 Jan 21;19(2):2148-2161. doi: 10.1021/acsnano.4c10701. Epub 2025 Jan 10.
Undifferentiated spermatogonia (Undiff-SPG) plays a critical role in maintaining continual spermatogenesis. However, the toxic effects and molecular mechanisms of maternal exposure to nanoplastics on offspring Undiff-SPG remain elusive. Here, we utilized a multiomics combined cytomorphological approach to explore the reproductive toxicity and mechanisms of polystyrene nanoplastics (PS-NPs) on offspring Undiff-SPG in mice after maternal exposure. The results indicated that PS-NPs decreased testosterone levels and reduced sperm concentration and quality in offspring male mice through maternal exposure. Moreover, PS-NPs could enter offspring Undiff-SPG, increase ROS levels, and decrease the viability of Undiff-SPG. According to the transcriptomics and proteomics analyses, PS-NPs caused offspring male mice Undiff-SPG inflammation by increasing the expression of /. Mechanistically, we found that inflammation induced overexpression of the transcription factor in Undiff-SPG, which suppressed the expression of and . Additionally, PS-NPs disrupted offspring spermatogenesis by inhibiting the // expression. Furthermore, PS-NPs reduced the Undiff-SPG autophagic flux by reducing the expression of /. In conclusion, maternal exposure to PS-NPs caused inflammation in offspring Undiff-SPG, which resulted in overexpression that could disrupt spermatogenesis and normal autophagy.
未分化精原细胞(Undiff-SPG)在维持持续的精子发生中起着关键作用。然而,母体暴露于纳米塑料对后代未分化精原细胞的毒性作用和分子机制仍不清楚。在此,我们采用多组学联合细胞形态学方法,探讨母体暴露后聚苯乙烯纳米塑料(PS-NPs)对小鼠后代未分化精原细胞的生殖毒性及其机制。结果表明,PS-NPs通过母体暴露降低了后代雄性小鼠的睾酮水平,降低了精子浓度和质量。此外,PS-NPs可进入后代未分化精原细胞,增加活性氧水平,并降低未分化精原细胞的活力。根据转录组学和蛋白质组学分析,PS-NPs通过增加/的表达导致后代雄性小鼠未分化精原细胞炎症。从机制上讲,我们发现炎症诱导未分化精原细胞中转录因子的过表达,从而抑制了和的表达。此外,PS-NPs通过抑制//的表达破坏了后代的精子发生。此外,PS-NPs通过降低/的表达减少了未分化精原细胞的自噬通量。总之,母体暴露于PS-NPs会导致后代未分化精原细胞炎症,进而导致过表达,从而破坏精子发生和正常自噬。