Arsenic trioxide (
As2O3) has recently received a great deal of attention because of its capacity to cause complete remission of
acute promyelocytic leukemia (APL). To evaluate possible toxicity on the male reproductive system during
arsenic therapy, male mice were used as a model. Outbred mice (ICR/CD1 and S-W, 6 weeks old) were subcutaneously administered
As2O3 continuously for 5 days, with a 2-day interval, for a period of 3 weeks.
As2O3 doses were 0, 0.15, 0.3, 1.5, and 3.0 mg/kg of
body weight, respectively. No mice died in any dosage group. Our data showed no significant changes in food consumption or in the weight of the body, liver, testis, or epididymis after
As2O3 treatment. Using histological observation to identify the stages of seminiferous tubules, we showed that
As2O3 treatment resulted in the inhibition of spermatogenesis. The frequency of mature seminiferous tubules (stages VII and VIII) was markedly decreased after
As2O3 treatment. A significant decrease in sperm motility and viability also was found with computer-assisted sperm analysis (CASA) and a SYBR14/PI staining assay. Using an
enzyme-linked
immunosorbent assay (ELISA), we found a significant decrease in levels of plasma
luteinizing hormone (LH) at a dose of 3.0 mg/kg
body weight. No significant difference was found in plasma
follicle-stimulating hormone (FSH) in all dosages. A significant decrease was found in plasma
testosterone in all dosages, but no difference in intratesticular
testosterone, with the exception of
As2O3 at a dose of 3.0 mg/kg
body weight. Moreover, there was a significant decrease in the levels of
mRNA involved in testicular
testosterone synthesis,
cytochrome P450 side chain cleavage (P450scc), 3beta-hydroxysteroid
dehydrogenase (3beta-HSD), and
cytochrome P450 17-alpha
hydroxylase/C17-20
lyase (
Cyp17). The use of immunohistological observation showed no obvious difference in the
testosterone level of Leydig cells of mice treated with
As2O3 at doses of 0.3 and 1.5 mg/kg
body weight. We concluded that
As2O3 treatment caused damage to sperm mobility and viability.
As2O3 treatment disturbed spermatogenesis via reducing gene expression of the key
enzymes in
testosterone synthesis.