Testicular cytotoxicity of DA-125, a new anthracycline anticancer agent, in rats

To assess the testicular cytotoxicity induced by DA-125, a new anthracycline anticancer agent, 50 male Sprague Dawley rats were randomly assigned to five groups, with 10 rats in each group, and were given different single intravenous doses of DA-125 at dose levels of 0, 6.25, 12.5, 25, and 50 mg/kg body weight. On Day 56 after treatment, all male rats were killed and necropsied. Parameters of testicular cytotoxicity included genital organ weights, testicular sperm head counts, epididymal sperm motility and morphology, repopulation index, epididymal index, and histopathologic examinations. At 25 and 50 mg/kg, the weights of testes, epididymides, and seminal vesicles were reduced dose-dependently, but prostate weight was not different among the groups. At 50 mg/kg, the number of testicular sperm heads was decreased. However, the motility and morphology of epididymal sperm were comparable to the control values. On histopathologic examination, atrophy of seminiferous tubules, loss or decrease of germ cells, formation of multinucleated giant cells, and/or vacuolization of Sertoli cells in the testis were observed at 25 and 50 mg/kg. In addition, decreased sperm content and increased degenerative germ cells in the ductus epididymis were also found. Some recovery of spermatogenesis was observed at 25 mg/kg, whereas a decline in the repopulation index was observed at 50 mg/kg, indicating that the surviving stem cells had become unable to produce differentiated germ cells to enter the spermatogenic pathway. There was no evidences of testicular cytotoxicity at 6.25 and 12.5 mg/kg. These results indicate that administration of a single dose of DA-12.5 (25 to 50 mg/kg) results in testicular damage in male Sprague-Dawley rats.