Effect of Cyclophosphamide on Oocyte and Follicle Number in Sprague-Dawley Rats, C57BL/6N and DBA/2N Mice

Oocyte and follicle destruction produced by cyclophosphamide was investigated in Sprague-Dawley (SD) rats, and inbred C57BL/6N (B6) and DBA/2N (D2) mice. Primordial oocytes were the most sensitive to destruction after intraperitoneal treatment with cyclophosphamide. A delayed decrease in the number of medium-sized follicles occurred between 1 and 2 weeks after treatment. No reduction in the number of large follicles was observed over the 3-week period of this experiment. Primordial oocyte destruction produced by cyclophosphamide occurred in a time-, dose-, strain-, and species-dependent fashion. The threshold for primordial oocyte/follicle destruction in B6 and D2 mice, and SD rats was less than 10, 40, and greater than 500 mg/kg, respectively. ED50S for primordial oocyte/follicle destruction were 49 and 137 mg/kg in B6 and D2 mice, respectively. The ED50 for oocyte destruction was greater than 500 mg/kg in SD rats. Primordial oocyte destruction occurred rapidly and was completed between 48 and 72 hours after treatment with cyclophosphamide in both murine strains. Oocyte destruction and premature ovarian failure is a significant side effect in women treated with alkylating agents. The rodent ovotoxicity model used in these experiments may be useful in elucidating mechanisms of ovotoxicity and evaluating treatment protocols designed to protect the ovary.