Lewis Sheena E M, Agbaje Ishola M
Reproductive Medicine, Queen's University of Belfast, Institute of Clinical Science, Grosvenor Road, Belfast, BT12 6BJ, Northern Ireland, UK.
Mutagenesis. 2008 May;23(3):163-70. doi: 10.1093/mutage/gem052. Epub 2008 Mar 5.
Infertility affects one in six couples in Europe during their reproductive years with dysfunctional sperm being one of the most common causes. Conventional semen analysis has proven variable and lacking in prognostic value so, over the past decade, more useful molecular fertility biomarkers have been explored. Among the tests showing most promise are those measuring sperm DNA quality. Sperm DNA damage has been closely associated with numerous indicators of reproductive health, including, fertilization, embryo quality, implantation, spontaneous abortion and childhood diseases. It therefore has great potential as a prognostic test for assisted reproductive treatment (ART), when couples are presenting with male infertility. Unlike somatic cells, sperm have a unique tightly compacted chromatin structure. Our group has modified the alkaline comet assay for use with sperm. Sperm DNA also differs from somatic cells in its high susceptibility to oxidative damage; this is largely due to the presence of abundant polyunsaturated fatty acids acting as substrates for reactive oxygen species (ROS) and its lack of repair mechanisms. Consequently, the effects of ROS and antioxidant protection on sperm DNA fragmentation have been widely investigated. In this review, the relationship between actual sperm DNA damage as determined by the alkaline comet assay and potential DNA damage as measured by DNA adduct testing will also be examined and the potential of routine clinical practices such as cryopreservation and prolonged incubation to induce further DNA damage was investigated. Finally, the usefulness of sperm DNA tests as prognostic markers and in particular, the opportunities and challenges provided by DNA testing in male fertility determination will be discussed.
在欧洲，六分之一的夫妇在生育年龄会受到不孕不育的影响，其中精子功能障碍是最常见的原因之一。传统的精液分析已被证明存在变数且缺乏预后价值，因此在过去十年中，人们探索了更有用的分子生育生物标志物。在显示出最大前景的检测方法中，有那些测量精子DNA质量的方法。精子DNA损伤与生殖健康的许多指标密切相关，包括受精、胚胎质量、着床、自然流产和儿童疾病。因此，当夫妇出现男性不育时，它作为辅助生殖治疗（ART）的预后检测具有巨大潜力。与体细胞不同，精子具有独特的紧密压缩染色质结构。我们的团队对碱性彗星试验进行了改进，使其适用于精子。精子DNA在对氧化损伤的高敏感性方面也与体细胞不同；这主要是由于存在大量多不饱和脂肪酸作为活性氧（ROS）的底物，并且其缺乏修复机制。因此，ROS和抗氧化保护对精子DNA片段化的影响已得到广泛研究。在这篇综述中，还将研究通过碱性彗星试验确定的实际精子DNA损伤与通过DNA加合物检测测量的潜在DNA损伤之间的关系，并研究冷冻保存和延长孵育等常规临床操作诱导进一步DNA损伤的可能性。最后，将讨论精子DNA检测作为预后标志物的有用性，特别是DNA检测在男性生育力测定中提供的机遇和挑战。
