Testicular function in adult rats treated with the alkylating agent chlorambucil

The effects of multiple treatments with the alkylating agent chlorambucil on testicular function in the adult Wistar rat were evaluated. Weekly treatment with doses of 2.5, 5, or 10 mg/kg produced no effect either on spermatogenesis or Leydig cell function. In contrast, doses of 8 or 10 mg/kg administered twice weekly induced damage to both spermatogenesis and probably the Leydig cells. A dose-dependent decrease in spermatogonial stem-cell survival was observed with these two regimens, as assessed by counts of repopulating tubule cross sections. Although serum testosterone remained unchanged, possible Leydig cell damage was indicated by an approximate twofold increase in serum LH following treatment with either 8 or 10 mg/kg of chlorambucil twice weekly. The present results demonstrate that multiple treatments with cytotoxic drugs can be used to model the testicular damage observed in man.