Cis-unsaturated fatty acids stimulate reactive oxygen species generation and lipid peroxidation in human spermatozoa
Cis-unsaturated fatty acids stimulate reactive oxygen species generation and lipid peroxidation in human spermatozoa
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DOI：
10.1210/jc.2006-1309
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发表时间：
2006-10-01
影响因子：
5.8
通讯作者：
McLaughlin, Eileen A.
中科院分区：
文献类型：
--
作者：
Aitken, R. John;Wingate, Jordana K.;McLaughlin, Eileen A.
背景：精子功能缺陷是人类不育的最大原因;然而，这种情况的病因学知之甚少。虽然氧化应激被认为是这种病理学的关键因素，但也有数据表明，有缺陷的人类精子含有异常高的顺式不饱和脂肪酸。本研究旨在探讨多不饱和脂肪酸对精子氧化应激的影响。方法：采用二氢乙锭和SYTOX绿色结合流式细胞术和高效液相色谱法，研究多不饱和脂肪酸对精子活性氧（ROS）的影响。结果：多不饱和脂肪酸对精子氧化应激的影响不明显。花生四烯酸（AA）诱导人精子产生ROS的时间和剂量依赖性增加，导致过氧化损伤的促进和精子活力的丧失。这种作用不能用AA代谢的环氧合酶或脂氧合酶途径的抑制剂、鱼藤酮、蛋白激酶C拮抗剂或质膜氧化还原系统的已知抑制剂来阻断。然而，ROS的产生可以触发与其他顺式不饱和脂肪酸，包括亚油酸和二十二碳六烯酸。饱和脂肪酸、不饱和脂肪酸的甲酯或其他两亲物都无效。然而，在一个无细胞系统中，AA可以触发氧化还原信号通过机制，被深深地破坏了diphenylene iodonium，flavoprotein inhibitors.Conclusions：过量的不饱和脂肪酸的存在下，有缺陷的人精子可能沉淀的氧化应激在男性不育症。
Context: Defective sperm function is the largest defined cause of human infertility; however, the etiology of this condition is poorly understood. Although oxidative stress is acknowledged as a key contributor to this pathology, there are also data indicating that defective human spermatozoa contain abnormally high amounts of cis-unsaturated fatty acids. This study investigated whether a causative relationship exists between these two attributes of impaired semen quality.Objective: The objective of this study was to determine whether polyunsaturated fatty acids can induce oxidative stress in human spermatozoa.Method: Dihydroethidium and SYTOX Green were used in conjunction with flow cytometry and HPLC to investigate reactive oxygen species (ROS) generation by human spermatozoa after fatty acid exposure.Results: Arachidonic acid (AA) induced a time- and dose-dependent increase in ROS generation by human spermatozoa that led to the promotion of peroxidative damage and a loss of sperm motility. This effect could not be blocked with inhibitors of the cyclooxygenase or lipoxygenase pathways of AA metabolism, rotenone, protein kinase C antagonists, or known inhibitors of plasma membrane redox systems. However, ROS generation could be triggered with other cis-unsaturated fatty acids including linoleic and docosahexaenoic acids. Saturated fatty acids, methyl esters of unsaturated fatty acids, or other amphiphiles were all ineffective. However in a cell-free system, AA could trigger a redox signal via mechanisms that were profoundly disrupted by diphenylene iodonium, a flavoprotein inhibitor.Conclusions: The presence of excess unsaturated fatty acids in defective human spermatozoa may precipitate the oxidative stress encountered in male infertility.