McClain R M, Downing J C
Department of Toxicology and Pathology, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Toxicol Appl Pharmacol. 1988 Mar 15;92(3):488-96. doi: 10.1016/0041-008x(88)90188-3.
A comprehensive study of male fertility and sperm production and function was performed in 20 control and 20 rats treated with ornidazole, a compound with trichomonacidal activity. Rats were treated for 4 weeks at dosages of 0 (control) and 400 mg/kg/day of ornidazole during which fertility was assessed by weekly matings. Testicular sperm production and epididymal sperm function were assessed in one-half of the rats while the reversibility of effects after a 2-week recovery period was assessed in the remaining half. Male rats treated with ornidazole were infertile during the second week of treatment. After 4 weeks of treatment, testicular and epididymal weights, testicular spermatid counts, epididymal sperm reserves, sperm morphology, and sperm viability were similar in treated and control rats. A quantitative assessment of epididymal sperm motility using a dark-field photomicroscope with a stroboscopic light source revealed that ornidazole markedly inhibited sperm motility. Although the percentage of nonmotile sperm was not substantially increased in treated rats, the vigor of tail movement was markedly decreased which resulted in decreased sperm velocity. Restoration of fertility and normal sperm motility and velocity were observed in the group of recovery rats assessed 2 weeks after the cessation of ornidazole treatment. It is concluded that ornidazole, at a high dosage of 400 mg/kg/day, produces infertility in male rats by inhibiting epididymal sperm motility in terms of decreased sperm velocity. These effects are rapidly reversible after the cessation of treatment.
对20只对照大鼠和20只接受奥硝唑治疗的大鼠进行了一项关于雄性生育能力、精子生成及功能的全面研究。奥硝唑是一种具有抗滴虫活性的化合物。大鼠分别以0（对照）和400毫克/千克/天的剂量接受为期4周的治疗，在此期间通过每周交配来评估生育能力。对一半的大鼠评估睾丸精子生成和附睾精子功能，而对另一半大鼠评估在2周恢复期后效应的可逆性。接受奥硝唑治疗的雄性大鼠在治疗的第二周出现不育。治疗4周后，治疗组和对照组大鼠的睾丸和附睾重量、睾丸精子细胞计数、附睾精子储备、精子形态及精子活力相似。使用带有频闪光源的暗视野显微镜对附睾精子活力进行定量评估发现，奥硝唑显著抑制精子活力。虽然在治疗组大鼠中不活动精子的百分比没有大幅增加，但尾部运动的活力明显下降，导致精子速度降低。在奥硝唑治疗停止2周后评估的恢复组大鼠中观察到生育能力以及精子活力和速度恢复正常。得出的结论是，奥硝唑以400毫克/千克/天的高剂量通过降低精子速度抑制附睾精子活力，从而使雄性大鼠不育。这些效应在治疗停止后可迅速逆转。
