Li Yan, Sheng Jie, Sha Jiahao, Han Xiaodong
Medical School, Nanjing University, Nanjing, Jiangsu 210093, PR China.
Reprod Toxicol. 2008 Nov-Dec;26(3-4):239-45. doi: 10.1016/j.reprotox.2008.09.004. Epub 2008 Sep 20.
The aim of this study was to investigate whether microcystin-LR, one of the most common cyanobacterial toxins has toxic effects on reproductive system in vivo or Leydig cells in vitro. Male rats were treated with MC-LR (i.p.) at a dose of 0, 5, 10 or15 microg/(kgday) for 28 days. Leydig cells were cultured with a culture medium including 0, 0.5, 5, 50 or 500 nM MC-LR. In vivo study, we observed exposure to 5 microg/(kgday) of MC-LR decreased the sperm motility, increasing the sperm abnormality rate, 15 microg/(kgday) of MC-LR led to the decrease of testis weight and sperm concentration, decreased the levels of serum testosterone, FSH and LH. The histological findings showed that the seminiferous tubules atrophied and obstructed. In vitro study evaluated MC-LR-induced toxicity and oxidative stress in Leydig cells. It was observed 50 and 500 nM MC-LR significantly decreased the cell viability, increasing the apoptotic DNA fragmentation, and increasing the ratio of necrotic cells. The Leydig cells exposed to MC-LR decreased testosterone production. 500 nM MC-LR increased ROS production, 50 or 500 nM MC-LR enhanced the lipid peroxidation. All Leydig cells exposed to MC-LR showed decreased SOD activity. The results of this study showed that the oxidative stress of MC-LR might lead to cytotoxicity, which may play an important role in cell apoptosis. Then could reduce the production of testosterone in Leydig cells and result in reproductive toxicity.
本研究的目的是调查最常见的蓝藻毒素之一微囊藻毒素-LR是否对体内生殖系统或体外睾丸间质细胞具有毒性作用。雄性大鼠腹腔注射0、5、10或15微克/(千克·天)剂量的微囊藻毒素-LR,持续28天。睾丸间质细胞在含有0、0.5、5、50或500纳摩尔微囊藻毒素-LR的培养基中培养。在体内研究中,我们观察到暴露于5微克/(千克·天)的微囊藻毒素-LR会降低精子活力,增加精子畸形率,15微克/(千克·天)的微囊藻毒素-LR会导致睾丸重量和精子浓度下降,血清睾酮、促卵泡激素和促黄体生成素水平降低。组织学结果显示生精小管萎缩和阻塞。体外研究评估了微囊藻毒素-LR对睾丸间质细胞的毒性和氧化应激作用。观察到50和500纳摩尔的微囊藻毒素-LR显著降低细胞活力,增加凋亡DNA片段化,并增加坏死细胞比例。暴露于微囊藻毒素-LR的睾丸间质细胞睾酮分泌减少。500纳摩尔的微囊藻毒素-LR增加活性氧生成,50或500纳摩尔的微囊藻毒素-LR增强脂质过氧化。所有暴露于微囊藻毒素-LR的睾丸间质细胞超氧化物歧化酶活性均降低。本研究结果表明,微囊藻毒素-LR的氧化应激可能导致细胞毒性,这可能在细胞凋亡中起重要作用。进而可能减少睾丸间质细胞中睾酮的产生并导致生殖毒性。