A systems toxicology approach to explore toxicological mechanisms of fluoroquinolones-induced testis injury.

ABSTRACT

The widespread use of fluoroquinolones (FQs) causes a serious risk to the environment and human health. Here, we evaluated the potential effect to induce testis damage by gatifloxacin (GAT) intragastrically treatment in mice (25, 50, and 100 mg/kg body weight per day for 7 days). We observed testicular weight, serum testosterone, antioxidant enzyme activity, and mRNA levels and pathways. Testicular histopathology indicated that GAT administration induced a dose-dependent spermatogenesis abnormality. At 50 mg/kg, GAT altered gene expression but did not change the weight and the levels of testosterone and antioxidant enzymes. These findings indicate that mRNA levels are more sensitive than weight and testosterone for detecting GAT testicular toxicity. We also found that GAT induced testicular damage by regulating the candidate genes associated with spermatogenesis, germ cell movement, testicular fibrosis, and reproductive axis development. This study enhances our perception of the mechanism of FQs-induced testicular toxicity and environmental effects. However, the molecular mechanism needs to be further researched.