Hikim A P, Lue Y H, Wang C, Reutrakul V, Sangsuwan R, Swerdloff R S
Department of Medicine, Harbor-UCLA Medical Center and Harbor-UCLA Research and Education Institute, Torrance, California 90509, USA.
J Androl. 2000 May-Jun;21(3):431-7.
A variety of active diterpene epoxides, including the triptolide (isolated from Tripterygium wilfordii) have been reported to cause infertility in male rats. Previously, we showed that oral administration of triptolide at a dosage of 100 microg/kg per body weight for 70 days completely inhibited fertility in male rats, with little or no demonstrable detrimental effect on spermatogenesis and Leydig cell function as determined by testicular light microscopic appearance and serum and intratesticular testosterone levels. Despite the apparent absence of effects on the testes, cauda epididymal sperm were abnormal, with complete cessation of sperm motility and some reduction in sperm numbers. This study was undertaken to provide additional insight into the subcellular sites and possible mechanisms of action of this compound using ultrastructural analysis of the testes and epididymidis. The most striking effect of triptolide treatment was observed in sperm in the epididymis. In rats rendered infertile with 100 microg/kg per body weight of triptolide daily for 70 days, virtually all cauda epididymal sperm exhibited complete absence of plasma membrane over the entire middle and principal piece, premature decondensation of the nuclei, and disorganization of the mitochondrial sheath with many vacuolated mitochondria. No ultrastructural differences in the epididymal epithelium were observed between control and triptolide-treated rats. The testes appeared to be mildly affected after triptolide treatment but exhibited only subtle ultrastructural defects in the germ cells. The findings of severe impairment of cauda epididymal sperm ultrastructure, along with minimal discernible abnormalities in the fine structural cytology of the testes, further suggest that the site of action of this compound is posttesticular and may be confined to the cauda epididymal sperm. However, we cannot rule out an effect of triptolide that occurs during germ cell maturation but is delayed in its manifestation or triggered at the rete testis and epididymal level.
据报道，多种活性二萜环氧化物，包括雷公藤内酯醇（从雷公藤中分离得到），可导致雄性大鼠不育。此前，我们发现，以每体重100微克/千克的剂量口服雷公藤内酯醇70天，可完全抑制雄性大鼠的生育能力，而根据睾丸光学显微镜外观以及血清和睾丸内睾酮水平测定，对精子发生和睾丸间质细胞功能几乎没有明显的有害影响。尽管对睾丸似乎没有影响，但附睾尾部精子异常，精子运动完全停止，精子数量有所减少。本研究旨在通过对睾丸和附睾进行超微结构分析，进一步深入了解该化合物的亚细胞作用位点和可能的作用机制。雷公藤内酯醇处理最显著的作用见于附睾中的精子。在每天以每体重100微克/千克的雷公藤内酯醇处理70天而不育的大鼠中，几乎所有附睾尾部精子在整个中段和主段均完全没有质膜，细胞核过早解聚，线粒体鞘紊乱，有许多空泡化的线粒体。在对照大鼠和经雷公藤内酯醇处理的大鼠之间，未观察到附睾上皮的超微结构差异。雷公藤内酯醇处理后，睾丸似乎受到轻度影响，但仅在生殖细胞中表现出细微的超微结构缺陷。附睾尾部精子超微结构严重受损，同时睾丸精细结构细胞学仅有微小的可辨异常，这些发现进一步表明该化合物的作用位点在睾丸后，可能局限于附睾尾部精子。然而，我们不能排除雷公藤内酯醇在生殖细胞成熟过程中发生作用，但表现延迟或在睾丸网和附睾水平触发的可能性。
