Evaluation of Recovery from Cyclophosphamide Testicular Toxicity in Rats

The testicular toxicity of cyclophosphamide (CP) in rats and recovery of normal spermatogenesis over an 8-week period were assessed. Male rats were administered 40mg/kg CP by gavage daily for 1 week and sacrificed at 1 day, 3 weeks, and 8 weeks after the cessation of treatment. The numbers of seminiferous epithelial cells were counted in the seminiferous tubules in stages II-III, V, VII, and XII of the spermatogenic cycle. Spermatogonia were decreased in number at 1 day after the last treatment, but most of the surviving spermatogonia including type A had proliferative activity, as demonstrated by PCNA staining. After 3-week recovery, the numbers of spermatogonia were improved, but the numbers of spermatocytes and round spermatids were reduced in some stages. Furthermore, focal substantial changes such as atrophy of seminiferous tubules were present in the testis. After 8-week recovery, the numbers of spermatogenic cells up to round spermatids were comparable to those in control specimens, and histopathologically no remarkable changes were observed in the testis. However, lower weights and sperm counts for testis and epididymis were still found at this time. These findings suggested that histopathological changes as subtle as decreased number of spermatogonia should be detected in evaluations of male chemical reproductive toxicity. Our findings also suggested that PCNA staining may be useful for predicting reversibility of testicular toxicity.