Silica nanoparticles induce reversible damage of spermatogenic cells via RIPK1 signal pathways in C57 mice

Abstract

The reproductive toxicity of silica nanoparticles (SiNPs) is well known, but the underlying mechanism is still not clear. To investigate the toxic mechanism of SiNPs on spermatogenic cells, 60 C57 male mice were randomly and equally divided into three groups (the control group, the saline control group, and the SiNPs group) with two observed time points (45 days and 75 days). The mice in the SiNPs group were administered with SiNPs 2 mg/kg diluted in normal saline, and the mice of the saline control group were given equivoluminal normal saline by tracheal perfusion every 3 days for 45 days (in total 15 times). The control group mice were bred without treatment. In each group, a half number of the mice were sacrificed on the 45th day after the first dose, and the remaining half were sacrificed on the 75th day. The results showed that SiNPs increased the malformation of sperms and decreased the motility and concentration of sperms in epididymis on the 45th day after the first dose. SiNPs induced oxidative stress in testis and led to apoptosis and necroptosis of the spermatogenic cells. Furthermore, SiNPs increased the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3 and RIPK3/MLKL on the 45th day after the first dose. However, compared with the saline control group, the index of sperms and the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3/RIPK3/MLKL showed no significant changes in the SiNPs group on the 75th day after the first dose. These data suggested that SiNPs could induce apoptosis and necroptosis in the spermatogenic cells by activating the RIPK1 pathway resulting from oxidative stress in male mice. SiNPs-induced damage recovered on the 75th day after the first dose, which suggested that SiNPs-induced toxicity is reversible.

<p>La₂O₃ Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice</p>

“…41,42 Previous studies showed that in vivo exposure of mice to NPs could induce oxidative stress, resulting in decreased SOD activity and increased MDA level in the testis, further confirming that NPs could induce ROS and inflammasome activation, thus inducing oxidative stress in the testis and lead to apoptosis and necroptosis of the spermatogenic cells. [43][44][45] The present study showed that in vivo exposure of mice to La 2 O 3 NPs could induce oxidative stress, leading to decreased SOD and CAT activities, and increased MDA levels in the testis, which was possibly caused by the toxic effects of oxidative stress and inflammatory mediators induced by La 2 O 3 NPs.…”

Pulmonary exposure to carbonaceous nanomaterials and sperm quality

“…Spermatogenesis is a steady state process and the ability to regenerate germ cell populations and recover functional spermatogonia after toxic insult are good. In fact, full recovery after an intratracheal instillation of 2 mg/kg of micelle coated silica NPs (57.66 nm) dispersed in saline has been observed [ 17 ]. Approximately thirty days after the last exposure, TEM images revealed that the silica particles could no longer be observed in the testis of C57 mice, and the reduced sperm motility and increased sperm abnormalities and apoptosis had been reversed [ 17 ].…”

“…In fact, full recovery after an intratracheal instillation of 2 mg/kg of micelle coated silica NPs (57.66 nm) dispersed in saline has been observed [ 17 ]. Approximately thirty days after the last exposure, TEM images revealed that the silica particles could no longer be observed in the testis of C57 mice, and the reduced sperm motility and increased sperm abnormalities and apoptosis had been reversed [ 17 ]. Potentially, induced effects may have been reversed in our study one week after the last instillation, when the tissue samples were collected.…”

“…The silica NPs decreased sperm concentration and motility, and increased sperm abnormalities. Testicular malondialdehyde and 3-nitrotyrosine levels were increased, whereas SOD activity was impaired; suggesting that the damage may have arisen due to oxidative stress in the testis [ 17 ].…”

Combined Subchronic Toxicity of Aluminum (III), Titanium (IV) and Silicon (IV) Oxide Nanoparticles and Its Alleviation with a Complex of Bioprotectors

“…The first two of the above species belong to the most widely manufactured and used nanomaterials [19] and thus frequently undergo toxicological assessment, though in vitro as a rule, and much less often in short-term animal experiments. The scientific literature of this kind dealing with TiO2-NP toxicity may be exemplified by [20][21][22][23][24][25][26][27][28][29][30][31][32], and that on SiO2-NP toxicity by [33][34][35][36][37][38][39][40][41][42][43][44][45][46] and numerous other sources. We could not find any long-term inhalation exposure studies of these nanomaterials right up to the point when we carried out such an experiment with an industrial aerosol containing a high proportion of nanoscale particles of predominantly amorphous SiO2 [47].…”