雷公藤多甙对早期雄性生殖细胞的影响-生物化学与分子生物学专业论文.docxVIP

PAGE PAGE 10 势，体外对 SSCs 中 H3K9me2 水平的检测得到相似结果。由此我们 推断 GTW 还可能通过抑制雄性生殖细胞中 H3K9 的表观遗传学修 饰来影响小鼠的精子发生过程，这为研究 GTW 抗生育机制开辟了 一条全新途径，也为全面研究该药物的作用机制和临床应用提供了 重要的理论依据。 关键词：精子发生，GTW，细胞凋亡，H3K9me2 The effect of Multiglycosides of Tripterygium wilfordii Hook. f. on early stage male germ cells ABSTRACT Multiglycosides of Tripterygium wilfordii Hook. f. (GTW), a Chinese herb-derived medicine used as the remedy of rheumatoid arthritis, allergic dermatitis and so on, could cause influence on the male reproductive system to the different degree. It has been shown that long-term medicine taking would lead to the reduction of the number of sperm and make sperm activity decreased. However, the fertility will recover gradually after the cessation of medication. Thus in recent years this medicine attracted many researchers’ attention and has been used for the research and development of male contraceptive. However, the underlying antifertility mechanism of GTW is still unclear. Previous studies focused on the late stage of spermatogenesis to research the mechanism. This study suggested that GTW could also affect the growth of spermatogonial stem cells (SSCs), which means that the anti-fertility effect of GTW could trace back to the initial stage of spermatogenesis. By the detection of histology and apoptosis we found a significant dosage-dependent decrease in the total number of germ cells in seminiferous tubules after the GTW treatment, and apoptotic cells were correspondingly increased from low-dosage to high-dosage group. In vitro detection on SSCs confirmed that GTW-triggered apoptosis could also take effects on SSCs, and was tending to be severe when the concentration or the treating time increased. We also detected the dimethylation level of histone H3 lysine 9 (H3K9me2) to examine the effect of GTW on the germline epigenetic state. Immunofluorescence assay showed that dimethylation level was declined in GTW-treated testes, and our in vitro detection on SSCs was corresponded to th