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

## TL;DR

This study shows that Tetrandrine protects male mice from reproductive damage caused by silica dust, both during early inflammation and later fibrosis stages.

## Contribution

The study reveals Tetrandrine's protective effects against silica-induced male reproductive toxicity and identifies time-dependent molecular mechanisms.

## Key findings

- Tetrandrine reduced testicular inflammation markers in mice exposed to silica at day 7.
- Tetrandrine decreased sperm deformity and fibrosis markers in silica-exposed mice at day 42.
- Transcriptome analysis showed distinct gene expression patterns at day 7 and day 42, indicating time-dependent injury mechanisms.

## Abstract

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.