The Protective Effect and Molecular Mechanism of Tetrandrine on Male Reproductive Damage Caused by Silicon Dioxide

The long-term inhalation of free silica dust causes silicosis-a prevalent occupational hazard-yet its systemic effect on male reproductive toxicity remains underexplored. Tetrandrine (Tet) is the only plant-derived anti-silicosis drug approved in China. This study investigates silica (SiO₂) -induced male reproductive damage and evaluates Tet's protective effects. Sixty male C57BL/6 mice (6-8 weeks) were divided into control, SiO₂ exposure, and SiO₂ + Tet groups. SiO₂ was administered via intranasal infusion and Tet via gavage. Mice were sacrificed at day 7 (male reproductive injury model corresponding to the pulmonary inflammation stage) and day 42 (male reproductive injury model corresponding to the pulmonary fibrosis stage). Analyses included sperm morphology, testicular transcriptome sequencing, RT-qPCR, and immunofluorescence. At day 7, SiO₂ exposure upregulated testicular inflammatory markers, which were partially mitigated by Tet. At day 42, SiO₂ increased sperm deformity and testicular fibrosis markers (fibronectin and vimentin); Tet intervention reduced these abnormalities. Transcriptome analysis revealed distinct gene expression patterns at day 7 versus day 42, indicating time-dependent injury mechanisms. Tetrandrine alleviates silica-induced reproductive damage in male mice, suggesting potential therapeutic applications for occupational silica exposure and expanding the understanding of silica toxicity beyond the respiratory system.