氧化应激检测在男性不育临床中的应用

活性氧 (ROS)在低浓度发生可以调节正常精子功能 ,而高浓度ROS危害精子的存活力和功能。ROS产生过量与抗氧化系统损伤会发生氧化应激 (OS)。目前认为损伤OS促进了一系列男性生殖功能的病理学改变。ROS介导的精子质膜过氧化损伤 ,可以解释在高比例的不育病人中观察到的精子功能缺陷。ROS产生过多也会破坏精子核内DNA的完整性。DNA碱基对OS敏感 ,这些结构的过氧化能引起碱基修饰、DNA链断裂以及染色质交联。由过量ROS诱发的DNA损伤会加速生殖细胞凋亡过程 ,导致与男性不育相关的精子计数降低 ,以及可以解释近半个世纪以来所观察到的精液质量明显下降现象。近 10年来 ,克里夫兰临床基金会的研究组已经查明了男性不育中OS的关键作用 ;研究的主要目的是将这些重要的知识从实验室转向临床应用。我们设计的研究目标 :①理解精液中OS发生的精确机制 ;②建立准确评估OS状态的实验 ,并进行质控研究 ;③检测OS与精子核DNA损伤之间的相关性 ;④鉴定精液OS评估对男性不育的临床意义

Utility of Oxidative Stress Test in the Male Infertility Clinic

The controlled generation of very low amounts of reactive oxygen species (ROS) appears to regulate normal sperm functions, while high levels of ROS endanger sperm viability and function. Oxidative stress (OS) develops as a consequence of excessive production of ROS and/or impaired antioxidant defense system. It is proposed that such OS precipitates a range of pathologies currently thought to afflict male reproductive function. ROS-mediated peroxidative damage to the sperm plasma membrane may account for defective sperm function observed in a high proportion of infertility patients. Excessive generation of ROS may also attack integrity of DNA in the sperm nucleus. DNA bases are susceptible to oxidative stress, and peroxidation of these structures can cause base modification, DNA strand breaks and chromatin cross-linking. DNA damage induced by excessive ROS may accelerate the process of germ cell apoptosis, leading to decline in sperm counts associated with male infertility, and may explain the apparent deterioration of semen quality observed during the past four to five decades. For almost a decade, our research team in the Cleveland Clinic Foundation has identified the critical role of OS in male infertility. The main objective of our research was to transfer this important knowledge from the research bench to clinical practice. We designed studies with the aims of: 1. understanding the exact mechanisms by which OS develops in semen, which we thought will help setup strategies to overcome the problem, 2. establishing assays for accurate assessment of OS status and running the quality control studies for this purpose, 3. testing the correlation between OS and sperm nuclear DNA damage, and 4. identifying the clinical significance of seminal OS assessment in male infertility practice.