Abstract
Reproductive toxicity of 1-Bromopropane (1-BP) was reported in animal studies. But the mechanism remains obscure. Oxidative metabolites of 1-BP through P450s and depletion of glutathione are thought to play important roles in 1-BP inducing toxicity. The present study aims to investigate the role of P450s in 1-BP inducing male reproductive toxicity, through controlling P450s activity by administration of 1-aminobenzotriazole (1-ABT). Mice pretreated with 1-ABT were exposed to 1-BP at 0, 50, or 250 ppm, while untreated mice were exposed at 0, 50, 250, or 1200 ppm, for 4 weeks. The results showed that in 1-ABT-untreated groups, sperm count and sperm motility were decreased by exposure to 1-BP at 250 ppm; histopathological study of testis showed that the count of retained elongated-spermatids at the basal region of post-spermiation-stage seminiferous tubules was increased in 50 and 250 ppm group; count of degenerating spermatocytes in stages IX, X, and XI seminiferous tubules was increased in 250 ppm group. These adverse effects were not found in 1-ABT-pretreated and 50 or 250 ppm 1-BP exposed groups. However, in 1200 ppm group, the effect of 1-ABT was limited and 1-BP exposure still resulted in obvious reproductive toxicity. For example, weights of reproductive organs were decreased; sperm count and motility were decreased; sperm abnormality was increased; spermatids retention and spermtocytes degeneration were increased. Additionally, depletion of spermatogenic cells and formation of Sertoli-cell-only seminiferous tubules were observed, which might suggest severe pathological changes; count of round spermatids in stage VII testicular seminiferous tubules was found decreased, which suggests round spermatid might be the target cells in 1-BP inducing male reproductive toxicity. In conclusion, these results indicate that P450s play important roles in 1-BP inducing male reproductive toxicity, especially at lower 1-BP exposure concentration. But higher concentration of 1-BP still results in obvious male reproductive toxicity, even when activity of P450s is inhibited.
