Ruan Qinli, Xu Yun, Xu Rui, Wang Jiaying, Hua Yongqing, Wang Meng, Duan Jinao
Center for Drug Safety Evaluation and Research, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Int J Mol Sci. 2017 Feb 21;18(2):464. doi: 10.3390/ijms18020464.
Previous studies have revealed that Triptolide damages female reproductive capacity, but the mechanism is unclear. In this study, we used to investigate the effects of Triptolide on the germline and explore its possible mechanisms. Our data show that exposure for 4 h to 50 and 100 mg/L Triptolide reduced fertility, led to depletion and inactivation of spermatids with the changes in the expression levels of related genes, and increased the number of unfertilized oocytes through damaging chromosomes and DNA damage repair mechanisms. After 24 and 48 h of the 4 h exposure to 50 and 100 mg/L Triptolide, we observed shrink in distal tip cells, an increase in the number of apoptotic cells, a decrease in the number of mitotic germ cells and oocytes in diakinesis stage, and chromatin aggregates in -1 oocytes. Moreover, expression patterns of the genes associated with mitotic germ cell proliferation, apoptosis, and oocyte quality were altered after Triptolide exposure. Therefore, Triptolide may damage fertility of nematodes by hampering the development of oocytes at different developmental stages. Alterations in the expression patterns of genes involved in oocyte development may explain the corresponding changes in oocyte development in nematodes exposed to Triptolide.
先前的研究表明雷公藤甲素会损害雌性生殖能力,但其机制尚不清楚。在本研究中,我们使用[具体方法]来研究雷公藤甲素对生殖系的影响并探索其可能的机制。我们的数据表明,暴露于50和100mg/L的雷公藤甲素4小时会降低生育能力,导致精子细胞耗竭和失活,相关基因表达水平发生变化,并通过破坏染色体和DNA损伤修复机制增加未受精卵母细胞的数量。在暴露于50和100mg/L雷公藤甲素4小时后的24和48小时,我们观察到远端末梢细胞萎缩,凋亡细胞数量增加,有丝分裂生殖细胞和减数分裂终变期卵母细胞数量减少,以及-1期卵母细胞中染色质聚集。此外,雷公藤甲素暴露后,与有丝分裂生殖细胞增殖、凋亡和卵母细胞质量相关的基因表达模式发生了改变。因此,雷公藤甲素可能通过阻碍不同发育阶段卵母细胞的发育来损害线虫的生育能力。参与卵母细胞发育的基因表达模式的改变可能解释了暴露于雷公藤甲素的线虫中卵母细胞发育的相应变化。