Cukierski M A, Sina J L, Prahalada S, Wise L D, Antonello J M, MacDonald J S, Robertson R T
Department of Safety Assessment, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Reprod Toxicol. 1991;5(4):353-62. doi: 10.1016/0890-6238(91)90094-v.
Oral administration of 80 mg/kg/day of finasteride, a potent specific inhibitor of 5 alpha-reductase, to sexually mature male Sprague-Dawley rats for 24 to 38 weeks caused an approximate 30% to 40% decrease in fertility. There were no effects on mating indices or implants per pregnant female. From the mating trials, a selected group of treated males with poor reproductive performance was compared to a selected group of control males with good reproductive performance. Observed matings showed no qualitative effects on mating behavior or ejaculation. However, finasteride-treated males did not form or formed small and improperly positioned copulatory plugs, which are required in rats to transport sperm into the uterus. Intrauterine insemination of epididymal sperm from males that were nonfertile by natural mating resulted in similar numbers of embryos and unfertilized oocytes recovered from controls and finasteride-treated males, confirming that there was no effect of finasteride on the ability of sperm to fertilize. Decreased fertility of finasteride-treated males was due to failure to form copulatory plugs and is related to decreased weight of seminal vesicles and prostate, an expected pharmacologic effect. Testes weight was unaffected. Decreased fertility in male rats after finasteride administration is considered a species specific effect. The mechanism of the decrease in rats is not likely to be relevant to species that do not form copulatory plugs.
对性成熟的雄性斯普拉格-道利大鼠口服给予80毫克/千克/天的非那雄胺（一种强效的5α-还原酶特异性抑制剂），持续24至38周，导致生育力下降约30%至40%。对每只怀孕雌性大鼠的交配指数或着床情况没有影响。在交配试验中，将一组生殖性能较差的经治疗雄性大鼠与一组生殖性能良好的对照雄性大鼠进行比较。观察到的交配行为对交配行为或射精没有定性影响。然而，经非那雄胺治疗的雄性大鼠没有形成或形成了小的且位置不当的交配栓，而在大鼠中交配栓是将精子输送到子宫所必需的。对自然交配不育的雄性大鼠的附睾精子进行子宫内授精，从对照大鼠和经非那雄胺治疗的大鼠中回收的胚胎和未受精卵母细胞数量相似，证实非那雄胺对精子受精能力没有影响。经非那雄胺治疗的雄性大鼠生育力下降是由于未能形成交配栓，并且与精囊和前列腺重量减轻有关，这是预期的药理作用。睾丸重量未受影响。非那雄胺给药后雄性大鼠生育力下降被认为是一种物种特异性效应。大鼠生育力下降的机制不太可能与不形成交配栓的物种相关。
