Hayashi M, Takizawa S, Fukatsu N, Imamura I, Shimura K, Horii I
Department of Toxicology and Pathology, Nippon Roche K. K., Research Center, Kanagawa, Japan.
J Toxicol Sci. 1995 Aug;20(3):281-96. doi: 10.2131/jts.20.281.
The toxicity of Etretinate, a retinoid compound, on the male reproductive system was studied in male rats. The drug was administered for four weeks at the dose levels of 0 (control: Vehicle, Peanut oil), 5 and 25 mg/kg/day. The animals were then allowed to mate, and their male reproductive functions and organs were examined in detail. No significant changes due to toxicity were observed in male reproductive functions and organs in the 5 mg/kg/day group after the 4-week treatment. In contrast, males in the 25 mg/kg/day group showed drug-related changes in their reproductive performance (decrease of mating ability and fertility rate), testosterone blood level, sperm head counts, sperm viability and number in the caudal epididymis, organ weight and in the histopathology of their reproductive organs (atrophy of seminiferous tubules, necrosis of spermatocytes and spermatids, vacuolation of nuclei of spermatocytes and spermatids). Even though Etretinate belong to the retinoid group of compounds, the changes seen in the 25 mg/kg/day group were almost the same as those observed in Vitamin A-deficient animals. In conclusion, there is a correlation between changes due to toxicity observed for parameters of male fertility and for histopathological evaluation of the testis of rats that receiving high dose, treatment with Etretinate for 4 weeks.
在雄性大鼠中研究了维甲酸类化合物依曲替酯对雄性生殖系统的毒性。以0（对照：赋形剂，花生油）、5和25mg/kg/天的剂量水平给药四周。然后让动物交配，并详细检查它们的雄性生殖功能和器官。在4周治疗后，5mg/kg/天组的雄性生殖功能和器官未观察到因毒性引起的显著变化。相比之下，25mg/kg/天组的雄性在生殖性能（交配能力和生育率下降）、睾酮血水平、精子头部计数、精子活力和附睾尾部精子数量、器官重量以及生殖器官组织病理学（生精小管萎缩、精母细胞和精子细胞坏死、精母细胞和精子细胞核空泡化）方面出现了与药物相关的变化。尽管依曲替酯属于维甲酸类化合物，但在25mg/kg/天组中观察到的变化与维生素A缺乏动物中观察到的变化几乎相同。总之，在接受高剂量依曲替酯治疗4周的大鼠中，观察到的雄性生育参数毒性变化与睾丸组织病理学评估之间存在相关性。
