Zhang Xue, Zhou Changyin, Li Weijian, Li Juan, Wu Wangjun, Tao Jingli, Liu Honglin
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Front Cell Dev Biol. 2020 Oct 8;8:582715. doi: 10.3389/fcell.2020.582715. eCollection 2020.
Microcystin-leucine arginine (MC-LR) is the most toxic cyanotoxin found in water bodies. Microcystins are produced as secondary products of cyanobacteria metabolism. They have a stable structure, and can bioaccumulate in living organisms. Humans and livestock who drink fresh water containing MC-LR can be poisoned. However, few studies have reported the effects of MC-LR exposure on livestock or human reproduction. In this study, we used porcine oocytes as a model to explore the effects of MC-LR on oocyte maturation, and studied the impact of vitamin C (VC) administration on MC-LR-induced meiosis defects. Exposure to MC-LR significantly restricted cumulus cell expansion and decreased first polar body extrusion. Further studies showed that MC-LR exposure led to meiosis arrest by disturbing cytoskeleton dynamics with MC-LR exposed oocytes displaying aberrant spindle organization, low levels of acetylate α-tubulin, and disturbed actin polymerization. Additionally, MC-LR exposure impaired cytoplasmic maturation by inducing mitochondria dysfunction. Moreover, MC-LR also produced abnormal epigenetic modifications, and induced high levels of oxidative stress, caused DNA damage and early apoptosis. The administration of VC provided partial protection from all of the defects observed in oocytes exposed to MC-LR. These results demonstrate that MC-LR has a toxic effect on oocyte meiosis through mitochondrial dysfunction-induced ROS, DNA damage and early apoptosis. Supplementation of VC is able to protect against MC-LR-induced oocyte damage and represents a potential therapeutic strategy to improve the quality of MC-LR-exposed oocytes.
微囊藻毒素 - 亮氨酸精氨酸(MC-LR)是水体中发现的毒性最强的蓝藻毒素。微囊藻毒素是蓝藻代谢的次级产物。它们结构稳定,可在生物体内生物累积。饮用含有MC-LR的淡水的人和牲畜可能会中毒。然而,很少有研究报道MC-LR暴露对牲畜或人类生殖的影响。在本研究中,我们以猪卵母细胞为模型,探讨MC-LR对卵母细胞成熟的影响,并研究维生素C(VC)给药对MC-LR诱导的减数分裂缺陷的影响。暴露于MC-LR会显著限制卵丘细胞扩展并降低第一极体排出率。进一步研究表明,MC-LR暴露通过扰乱细胞骨架动力学导致减数分裂停滞,暴露于MC-LR的卵母细胞显示出异常的纺锤体组织、低水平的乙酰化α-微管蛋白和紊乱的肌动蛋白聚合。此外,MC-LR暴露通过诱导线粒体功能障碍损害细胞质成熟。此外,MC-LR还产生异常的表观遗传修饰,并诱导高水平的氧化应激,导致DNA损伤和早期凋亡。VC给药为暴露于MC-LR的卵母细胞中观察到的所有缺陷提供了部分保护。这些结果表明,MC-LR通过线粒体功能障碍诱导的活性氧、DNA损伤和早期凋亡对卵母细胞减数分裂产生毒性作用。补充VC能够预防MC-LR诱导的卵母细胞损伤,并代表一种潜在的治疗策略,以提高暴露于MC-LR的卵母细胞的质量。