Delayed effects of doxorubicin on spermatogenesis and endocrine function in rats

Doxorubicin was administered to adult male Wistar rats (1 mg/kg body weight, three times per week, for one, two, three, or four weeks) in order to examine testicular and reproductive endocrine toxicity 56 days after treatment. Doxorubicin treatment produced persistent dose-related reductions in testis, epididymis, and seminal vesicle weights, but did not alter ventral prostate weight. Testis and serum testosterone levels were not significantly affected by treatment, but serum LH was increased after treatment, and binding of iodinated hCG to testicular LH receptors was reduced. Serum FSH was elevated by the two lower total administered doses, but was not different from controls after treatment with the two higher total doses. There was clear histologic evidence of dose-dependent damage to the seminiferous tubules, which was reflected by decreased testicular and epididymal sperm content and by reductions in the stem-cell survival index. These results indicate that doxorubicin produces significant and persistent damage to the endocrine and spermatogenic compartments of the testis.