Reproductive toxicity investigation of silica nanoparticles in male pubertal mice

Silica nanoparticles (SiNPs), one of the most produced nanoparticles (NPs) in the world, are used in all aspects of life. The increased application of SiNPs, especially in medicine, has raised considerable concern regarding their toxicological impact. Previous studies have shown that SiNPs can pass through the reproductive barrier and cause reproductive organ dysfunction by destroying Sertoli cells, Leydig cells, and germ cells. However, little is known about the mechanism of SiNPs-induced reproductive toxicity. In the present study, 5-week-old male mice were intraperitoneally administered SiNPs per day for 1 week at a dose of 0.2 mg per mouse. The results showed that SiNPs could cause damage to the structure of the testis and the epididymis and change the reproductive organ coefficients, leading to decreases of 56.1% and 55.3% in the rates of sperm concentration and motility and an increase of 168.8% in the rate of sperm abnormality. Moreover, the serum testosterone level obviously decreased from 18.77 to 5.23 µg/ml after exposure, and the transcription statuses of some key genes involved in the synthesis and transport of testosterone in the testis were also affected. Additional experiments showed that SiNPs exposure during puberty induced oxidative stress and an inflammatory response, as shown by the changed activity of superoxide dismutase (SOD), increased contents of malondialdehyde (MDA), and excess expression of proinflammatory factors, including TNF-α and IL-1β. Furthermore, the administration of SiNPs caused DNA damage and cell apoptosis, which were presented by the increased apoptotic cells in the sections of testis and epididymis and activation of the TNF-α/TNFR I-mediated pro-apoptotic pathway. In conclusion, these results indicate that SiNPs exposure during puberty significantly damaged the structure and function of the testis and epididymis by inducing oxidative stress and cell apoptosis. This study provides novel insight into SiNPs-induced reproductive toxicity during puberty, which warrants a more careful assessment of SiNPs before their application in juvenile supplies.