Morphological evaluation of cyclophosphamide testicular toxicity in rats using quantitative morphometry of spermatogenic cycle stages.

The testicular toxicity of cyclophosphamide (Cp) in rats was evaluated by quantitative morphometry of spermatogenic cycle stages. Nine-week-old male Sprague-Dawley rats in Group 1 were given a single oral administration of 100 mg/kg of Cp, and were sacrificed at 1, 7, 14 and 21 days thereafter. Rats in Group 2 were orally given 100 mg/kg/day of Cp for 2 days, followed by 50 mg/kg/day for the next 3 days, and were sacrificed at 1 and 4 days after the last administration. The numbers of seminiferous epithelia were counted in the seminiferous tubules of stages II, V, VII and XII of the spermatogenic cycle. The data were expressed as numbers of spermatogenic cells per Sertoli cells per seminiferous tubule cross section. Animals in Group 1 showed decreased preleptotene spermatocytes at Day 7, decreased zygotene spermatocytes at Day 14, and decreased pachytene spermatocytes at Day 21. In group 2, testicular toxicity could also be clearly detected by this morphometric approach. The present morphometric study thus indicates that testicular toxicity can be detected from Day 7 even after a single administration of Cp.