Effect of Prograf (FK506) on spermatogenesis in rats
Effect of Prograf (FK506) on spermatogenesis in rats
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DOI：
10.1016/0300-483x(96)03312-4
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发表时间：
1996-05-17
期刊：
影响因子：
4.5
通讯作者：
Ohara, K
中科院分区：
文献类型：
--
作者：
Hisatomi, A;Fujihira, S;Ohara, K
以1或3 mg/kg/d的剂量皮下给予雄性成年大鼠FK 506，持续2周，以研究其对精子发生的影响。普乐可复剂量依赖性地降低精子计数和活力，但不影响大鼠血清中的睾酮水平。在组织学上，在给予Bisoff的所有大鼠中，睾丸、精囊或前列腺均无异常变化，但在3 mg/kg/天剂量组的附睾中观察到导管内嗜酸性小球，可能是精子细胞变性。停药后精子计数和活力恢复至对照水平。结果表明，Prograf通过直接作用于附睾中的精子而减少精子数量和活力，但不会减少睾丸中精子的产生。环孢素A（CsA）在本研究中被用作参比药物。30 mg/kg/天的CsA也降低了精子计数和活力，停药后这些变化恢复。将接受2周BMPF给药的雄性动物与未给药的雌性动物交配，以研究其对雄性动物生育能力的影响。BAF不影响交配或生育力指数，但在3 mg/kg/天剂量组中观察到与着床丢失相关的活胎数量减少。认为这些变化是由于精子计数和活力降低所致，尽管1 mg/kg/天的BAF（临床剂量的5-10倍）不影响任何生育力参数，包括着床指数。
Prograf(FK506) was given to male mature rats in a daily subcutaneous dose of 1 or 3 mg/kg/day for 2 weeks to investigate its effect on spermatogenesis. Prograf dose-dependently decreased sperm counts: and motility, but did not affect testosterone level in the serum of rats. Histopathologically, there were no abnormal changes in the testis, seminal vesicle or prostate in any rats dosed with Prograf, but intra-ductal eosinophilic globules, probably degeneration of the sperm cells, were observed in the epididymis of the 3 mg/kg/day group. Sperm counts and motility returned to the control levels after stopping of the drug. The results indicate that Prograf decreased sperm counts and motility through direct action on the sperm in the epididymis, but not the production of sperm in the testis. Cyclosporine A (CsA) was used as the reference drug in the present study. Thirty mg/kg/day of CsA also decreased sperm counts and motility, and stopping of the drug led to the recovery of these changes. The males dosed with Prograf for 2 weeks were mated with non-dosed females to investigate its effect on the fertility potential of the males. Prograf did not affect copulation or fertility index, but a decrease in the number of live fetuses associated with implantation loss was observed in the 3 mg/kg/day group. The changes were considered to be due to the decrease of sperm counts and motility, although 1 mg/kg/day of Prograf, 5-10 times the clinical dose, did not affect any fertility parameters including implantation index.