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Silica nanoparticles inducing the apoptosis via microRNA-450b-3p targeting MTCH2 in mice and spermatocyte cell
Guiqing Zhou1, Jianhui Liu1, Xiangyang Li1
1Department 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.
Abstract:
Silica nanoparticles (SiNPs) could cause reproductive toxicity. The role of miRNAs in reproductive toxicity induced by SiNPs is still ambiguous. The present study was designed to investigate the role of miRNA-450 b-3p. In vivo, 40 male mice were randomly divided into control, and 20 mg/kg SiNPs groups. The mice were administrated by tracheal perfusion for 35 days. In vitro, spermatocyte cells (GC-2spd cells) were divided into 6 groups: 0 μg/mL SiNPs groups, 5 μg/mL SiNPs groups, 5 μg/mL SiNPs + miRNA-450 b-3p mimic transfection group, 5 μg/mL SiNPs + miRNA-450 b-3p mimic negative control group, 5 μg/mL SiNPs + miRNA-450 b-3p inhibitor transfection group, and 5 μg/mL SiNPs + miRNA-450 b-3p inhibitor negative control group. The results showed that SiNPs induced the apoptosis of spermatogenic cells, decreased the quantity and quality of the sperm, reduced the expressions of miR-450 b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, the mimic of miRNA-450 b-3p reversed the decrease of viability and the increase of apoptosis rate and significantly antagonized the expression enhancements of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3 induced by SiNPs, while inhibitor of miRNA-450 b-3p further promoted the effects induced by SiNPs. The result suggested that SiNPs could inhibit the miR-450 b-3p expression resulting in activation of the mitochondrial apoptosis signaling pathways by regulating the MTCH2 in the spermatocyte cells and, thus, induce the reproductive toxicity.
Insights
Silica nanoparticles (SiNPs) cause male reproductive toxicity by decreasing miR-450b-3p expression, leading to increased spermatogenic cell apoptosis. Restoring miR-450b-3p levels in vitro mitigates SiNP-induced damage.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Molecular Biology
Background:
- Silica nanoparticles (SiNPs) are increasingly recognized for their potential to induce reproductive toxicity.
- The precise molecular mechanisms, particularly the role of microRNAs (miRNAs), in SiNP-induced reproductive harm remain incompletely understood.
Purpose of the Study:
- To investigate the role of miRNA-450b-3p in silica nanoparticle-induced reproductive toxicity in male mice.
- To elucidate the molecular pathways involved in SiNP-mediated damage to spermatogenic cells.
Main Methods:
- In vivo study: Male mice were exposed to SiNPs via tracheal perfusion for 35 days.
- In vitro study: Spermatocyte (GC-2spd) cells were treated with SiNPs and transfected with miRNA-450b-3p mimics or inhibitors.
- Analysis included sperm parameters, cell viability, apoptosis rates, and protein expression levels (MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3).
Main Results:
- SiNPs exposure in vivo led to decreased sperm quantity and quality, increased spermatogenic cell apoptosis, reduced miR-450b-3p expression, and elevated pro-apoptotic protein levels in testes.
- In vitro, SiNPs induced GC-2spd cell apoptosis and decreased viability, correlating with reduced miR-450b-3p and increased apoptosis-related proteins.
- MiRNA-450b-3p mimic transfection counteracted SiNP-induced apoptosis and protein changes, while an inhibitor exacerbated them.
Conclusions:
- SiNPs induce male reproductive toxicity by downregulating miR-450b-3p expression.
- This downregulation activates mitochondrial apoptosis pathways, partly through regulating MTCH2 in spermatocyte cells.
- MiRNA-450b-3p plays a protective role against SiNP-induced reproductive toxicity.
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