Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
Yanjing Medical College Capital Medical University, Beijing, China.
Environ Pollut. 2020 Oct;265(Pt A):114974. doi: 10.1016/j.envpol.2020.114974. Epub 2020 Jun 9.
Silica nanoparticles (SiNPs) can reduce both quality and quantity of sperm via inhibiting the progress of meiosis and mitosis and inducing apoptosis of spermatogenic cells, however, their specific mechanism and effects on the later stage of spermatogenesis are still unclear. To investigate the effects of SiNPs on the reproductive system, male mice were treated with SiNPs (0, 1.25, 5 and 20 mg/kg.bw) via intratracheal instillation once every 3 days and for a total of 15 days. Results revealed that exposure to SiNPs induced reduction in the rate of sperm activity, histological abnormalities in seminiferous epithelium as well as apoptosis of spermatogenic cells, which are associated with decreased level of Lethal (3) malignant brain tumor like 2 (L3MBTL2) and activation of DNA damage-p53-mitochondrial apoptosis pathways. Moreover, reduction in L3MBTL2 level caused by SiNPs also led to the lower expression of RNF8-ubH2A/ubH2B pathway, thus resulting in incomplete histone-to-protamine exchange. These results suggest that the inhibition of L3MBTL2 expression caused by SiNPs not only activates DNA damage-p53-mitochondrial apoptosis pathway leading to the apoptosis of spermatogenic cells, but also inhibits RNF8-ubH2A/ubH2B pathway resulting in incomplete histone-to-protamine exchange, thereby affected spermatogenesis. This indicates that L3MBTL2 plays an important role in reproductive toxicity of males caused by SiNPs.
硅纳米颗粒 (SiNPs) 可通过抑制减数分裂和有丝分裂的进程以及诱导精原细胞凋亡来减少精子的数量和质量，但它们对精子发生后期阶段的具体作用机制仍不清楚。为了研究 SiNPs 对生殖系统的影响，雄性小鼠通过气管内滴注方式接受 SiNPs（0、1.25、5 和 20mg/kg.bw）处理，每 3 天处理 1 次，共处理 15 天。结果表明，SiNPs 暴露会降低精子活力，导致生精上皮组织形态异常和精原细胞凋亡，这与 Lethal（3）恶性脑肿瘤样 2（L3MBTL2）水平降低以及 DNA 损伤-p53-线粒体凋亡途径的激活有关。此外，SiNPs 引起的 L3MBTL2 水平降低也导致 RNF8-ubH2A/ubH2B 途径表达减少，从而导致组蛋白到鱼精蛋白的转换不完全。这些结果表明，SiNPs 抑制 L3MBTL2 表达不仅会激活 DNA 损伤-p53-线粒体凋亡途径导致精原细胞凋亡，还会抑制 RNF8-ubH2A/ubH2B 途径导致组蛋白到鱼精蛋白的转换不完全，从而影响精子发生。这表明 L3MBTL2 在 SiNPs 引起的雄性生殖毒性中发挥重要作用。
