Shiromizu K, Thorgeirsson S S, Mattison D R
Pediatr Pharmacol (New York). 1984;4(4):213-21.
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.
在斯普拉格-道利（SD）大鼠以及近交系C57BL/6N（B6）和DBA/2N（D2）小鼠中，研究了环磷酰胺对卵母细胞和卵泡的破坏作用。经腹腔注射环磷酰胺后，原始卵母细胞对破坏最为敏感。治疗后1至2周，中等大小卵泡数量出现延迟减少。在本实验的3周期间，未观察到大型卵泡数量减少。环磷酰胺导致的原始卵母细胞破坏呈现出时间、剂量、品系和物种依赖性。B6和D2小鼠以及SD大鼠中原始卵母细胞/卵泡破坏的阈值分别小于10、40和大于500 mg/kg。B6和D2小鼠中原始卵母细胞/卵泡破坏的半数有效剂量（ED50）分别为49和137 mg/kg。SD大鼠中卵母细胞破坏的ED50大于500 mg/kg。在两种小鼠品系中，环磷酰胺治疗后48至72小时内，原始卵母细胞破坏迅速发生并完成。卵母细胞破坏和卵巢早衰是接受烷化剂治疗的女性的一种显著副作用。这些实验中使用的啮齿动物卵巢毒性模型可能有助于阐明卵巢毒性机制，并评估旨在保护卵巢的治疗方案。
