Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology
Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology
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DOI：
10.1016/j.bcp.2016.09.015
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发表时间：
2016-12-01
影响因子：
5.8
通讯作者：
De Iuliis, G. N.
中科院分区：
文献类型：
--
作者：
Aitken, R. J.;Muscio, L.;De Iuliis, G. N.
在辅助生殖技术中保护人类精子免受氧化应激的需要，促使人们详细分析酚类化合物对这些细胞功能完整性的影响。对16种化合物的研究揭示了令人惊讶的各种负面影响，包括：（i）线粒体膜电位的损失（Δ psi m）通过与渗透性转换孔的打开无关但与硫醇表达的减少相关的机制，（ii）细胞内还原型谷胱甘肽的下降，（iii）刺激促氧化剂活性，包括诱导从线粒体和非线粒体来源产生ROS，（iv）刺激脂质过氧化，（v）产生氧化性DNA损伤，和（vi）受损的精子活力。对于大多数的多酚化合物检查，运动性的损失是渐进的，并与脂质过氧化的诱导高度相关（r = 0.889）。例外的是棉酚，其诱导的运动性迅速丧失，由于其固有的烷基化活性，其中一个后果是在精子尾部的羧甲基赖氨酸表达显着减少，翻译后修饰，是已知的在调节精子运动中发挥关键作用。在低于100 μ M的剂量下，似乎对精子没有不利影响的唯一多酚是白藜芦醇、染料木素和THP。因此，这些化合物可能在临床环境中具有一定的治疗潜力。(C)2016 Elsevier Inc. All rights reserved.
The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Delta psi m) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non-mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r = 0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100 mu M. These compounds could, therefore, have some therapeutic potential in a clinical setting. (C) 2016 Elsevier Inc. All rights reserved.