Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and p...Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action.Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 ug.kg～(-l).d～(-1) for 5 weeks, fertility wasassessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes werealso performed. Results: Administration of tripchlorolide at 50 ugg.kg～(-l)-d～(-1) for 3 weeks did not influence the fertilityof male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected fromcauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and α-glucosidase content in the epididymal fluid were decreasd. There were no significant differences in α-glucosidase andacid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious mor-phological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosomecurving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In tesficular homogenates,tripchlorolide had no influence on the lactate dehydrogenase-C_4 (LDH-C_4) and hyaluronidase activities. No apparentlesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed,tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and tes-ticular and epididymal spermatozoa. (Asian J Androl 1999 Sep ; 1: 121 - 125)展开更多
DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular detail...DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular details about the correlation between the checkpoint and regulation of DNA replication are still unclear. To investigate the connections between DNA replication and DNA damage checkpoint, a DNA-damage reagent, tripchlorolide, was applied to CHO (Chinese ovary hamster) cells at early- or middle-stages of the S phase. The early-S-phase treatment with TC significantly delayed the progression of the S phase and caused the phosphorylation of the Chkl checkpoint protein, whereas the middle-S-phase treatment only slightly slowed down the progression of the S phase. Furthermore, the analysis of DNA replication patterns revealed that replication pattern II was greatly prolonged in the cells treated with the drug during the early-S phase, whereas the late-replication patterns of these cells were hardly detected, suggesting that the activation of the intra-S-phase checkpoint inhibits the late-origin firing of DNA replication. We conclude that cells at different stages of the S phase are differentially sensitive to the DNA-damage reagent, and the activation of the intra-S phase checkpoint blocks the DNA replication progression in the late stage of S phase.展开更多
文摘Aim: To further evaluate the antifertility effects of tripchorolide, a derivative of triptolide produced at the extraction pro-cedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action.Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 ug.kg～(-l).d～(-1) for 5 weeks, fertility wasassessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes werealso performed. Results: Administration of tripchlorolide at 50 ugg.kg～(-l)-d～(-1) for 3 weeks did not influence the fertilityof male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected fromcauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and α-glucosidase content in the epididymal fluid were decreasd. There were no significant differences in α-glucosidase andacid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious mor-phological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosomecurving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In tesficular homogenates,tripchlorolide had no influence on the lactate dehydrogenase-C_4 (LDH-C_4) and hyaluronidase activities. No apparentlesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed,tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and tes-ticular and epididymal spermatozoa. (Asian J Androl 1999 Sep ; 1: 121 - 125)
基金This work was supported by a grant from the National Natural Science Foundation of China(No.30230110)a special grant from the Major State Basic Research Pro-gram of China(No.G1999053901)a grant from the Chinese Academy of Sciences(No.KSCX2-SW-203)to Jia Rui WU.
文摘DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular details about the correlation between the checkpoint and regulation of DNA replication are still unclear. To investigate the connections between DNA replication and DNA damage checkpoint, a DNA-damage reagent, tripchlorolide, was applied to CHO (Chinese ovary hamster) cells at early- or middle-stages of the S phase. The early-S-phase treatment with TC significantly delayed the progression of the S phase and caused the phosphorylation of the Chkl checkpoint protein, whereas the middle-S-phase treatment only slightly slowed down the progression of the S phase. Furthermore, the analysis of DNA replication patterns revealed that replication pattern II was greatly prolonged in the cells treated with the drug during the early-S phase, whereas the late-replication patterns of these cells were hardly detected, suggesting that the activation of the intra-S-phase checkpoint inhibits the late-origin firing of DNA replication. We conclude that cells at different stages of the S phase are differentially sensitive to the DNA-damage reagent, and the activation of the intra-S phase checkpoint blocks the DNA replication progression in the late stage of S phase.
