Silica nanoparticles induces sperm granuloma formation and blood-epididymal barrier disruption via the p38 MAPK pathway in mice.

Previous researches have demonstrated that the silica nanoparticles (SiNPs), which are widely used in all aspects of life, are hazardous to the male reproductive system. However, the cellular and molecular mechanism underlying SiNPs toxicity to the epididymis remain unclear. In this present study, a total of 60 male mice were separated into 4 groups and then treated to SiNPs for 7 consecutive days at a dose of 0, 2.5, 10, and 20 mg/kg body weight. The results showed that SiNPs could alter the histological structure of epididymis and induce sperm granuloma formation, leading to decreased sperm quality and quantity. In addition, the ultrastructure and permeability of blood-epididymal barrier (BEB) were impaired after exposure to SiNPs, and a significant downregulation of integral membrane proteins at the BEB was detected. SiNPs were also found to raise the percentage of macrophages in the epithelium and interstitium of the epididymis, followed by increased expression of pro-inflammatory molecules including TNF α, IL-1ß, and IL-6. Meanwhile, SiNPs induced oxidative stress in epididymis, as shown by the markedly elevated generation of reactive oxygen species (ROS) and malondialdehyde (MDA) and upregulated activity of superoxide dismutase (SOD). Further study showed that SiNPs activated the p38 MAPK signaling pathway, which accelerated clathrin-mediated endocytosis of integral membrane proteins and perturb vesicular trafficking. Taken together, exposure to SiNPs could induce sperm granuloma formation and impair the integrity of BEB in mice through activating the p38 MAPK pathway.

Silica nanoparticles cause spermatogenesis dysfunction in mice via inducing cell cycle arrest and apoptosis.

The widespread use of silica nanoparticles (SiNPs) has increased the risk of human exposure, which raised concerns about their adverse effects on human health, especially the reproductive system. Previous studies have shown that SiNPs could cause damage to reproductive organs, but the specific mechanism is still unclear. In this study, to investigate the underlying mechanism of male reproductive toxicity induced by SiNPs, 40 male mice at the age of 8 weeks were divided into two groups and then intraperitoneally injected with vehicle control or 10 mg/kg SiNPs per day for one week. The results showed that SiNPs could damage testicular structure, perturb spermatogenesis and reduce serum testosterone levels, leading to a decrease in sperm quality and quantity. In addition, the ROS level in the testis of exposed mice was significantly increased, followed by imbalance of the oxidative redox status. Further study revealed that exposure to SiNPs led to cell cycle arrest and apoptosis, as shown by downregulation of the expression of positive cell cycle regulators and the activation of TNF-α/TNFR Ⅰ-mediated apoptotic pathway. The results demonstrated that SiNPs could cause testicles injure via inducing oxidative stress and DNA damage which led to cell cycle arrest and apoptosis, and thereby resulting in spermatogenic dysfunction.