Rashki Ghaleno Leila, Alizadeh AliReza, Drevet Joël R, Shahverdi Abdolhossein, Valojerdi Mojtaba Rezazadeh
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran 16635-148, Iran.
Faculty of Medicine, GReD Institute, INSERM U1103-CNRS UMR6293-Université Clermont Auvergne, CRBC Building, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France.
Antioxidants (Basel). 2021 Jan 12;10(1):97. doi: 10.3390/antiox10010097.
One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm cell specific cytologic and metabolic features (no cytoplasm left and cells unable to mount stress responses) make it the cell type in metazoans most susceptible to oxidative damage. In particular, oxidative damage to the spermatozoa genome is an important issue and a cause of male infertility, usually associated with single- or double-strand paternal DNA breaks. Various methods of detecting sperm DNA fragmentation have become important diagnostic tools in the prognosis of male infertility and such assays are available in research laboratories and andrology clinics. However, to date, there is not a clear consensus in the community as to their respective prognostic value. Nevertheless, it is important to understand that the effects of oxidative stress on the sperm genome go well beyond DNA fragmentation alone. Oxidation of paternal DNA bases, particularly guanine and adenosine residues, the most sensitive residues to oxidative alteration, is the starting point for DNA damage in spermatozoa but is also a danger for the integrity of the embryo genetic material independently of sperm DNA fragmentation. Due to the lack of a spermatozoa DNA repair system and, if the egg is unable to correct the sperm oxidized bases, the risk of de novo mutation transmission to the embryo exists. These will be carried on to every cell of the future individual and its progeny. Thus, in addition to affecting the viability of the pregnancy itself, oxidation of the DNA bases in sperm could be associated with the development of conditions in young and future adults. Despite these important issues, sperm DNA base oxidation has not attracted much interest among clinicians due to the lack of simple, reliable, rapid and consensual methods of assessing this type of damage to the paternal genome. In addition to these technical issues, another reason explaining why the measurement of sperm DNA oxidation is not included in male fertility is likely to be due to the lack of strong evidence for its role in pregnancy outcome. It is, however, becoming clear that the assessment of DNA base oxidation could improve the efficiency of assisted reproductive technologies and provide important information on embryonic developmental failures and pathologies encountered in the offspring. The objective of this work is to review relevant research that has been carried out in the field of sperm DNA base oxidation and its associated genetic and epigenetic consequences.
男性不育的一个重要原因是氧化应激及其对精子结构和功能的破坏作用。精子膜富含多不饱和脂肪酸的特殊组成，以及由于精子细胞特定的细胞学和代谢特征（没有剩余细胞质且细胞无法产生应激反应）导致精子DNA容易受到氧化损伤，使其成为后生动物中最易受氧化损伤的细胞类型。特别是，精子基因组的氧化损伤是一个重要问题，也是男性不育的一个原因，通常与父本DNA的单链或双链断裂有关。检测精子DNA片段化的各种方法已成为男性不育预后的重要诊断工具，此类检测在研究实验室和男科诊所均可进行。然而，迄今为止，对于它们各自的预后价值，学界尚未达成明确共识。尽管如此，重要的是要明白氧化应激对精子基因组的影响远不止于DNA片段化。父本DNA碱基的氧化，特别是鸟嘌呤和腺苷残基，这两种对氧化改变最敏感的残基，是精子DNA损伤的起点，但独立于精子DNA片段化之外，对胚胎遗传物质的完整性也是一种威胁。由于缺乏精子DNA修复系统，并且如果卵子无法纠正精子氧化的碱基，就存在将新发突变传递给胚胎的风险。这些突变将传递给未来个体及其后代的每个细胞。因此，除了影响妊娠本身的存活率外，精子中DNA碱基的氧化还可能与年轻人和未来成年人疾病的发生有关。尽管存在这些重要问题，但由于缺乏简单、可靠、快速且一致认可的评估父本基因组此类损伤的方法，精子DNA碱基氧化尚未引起临床医生的太多关注。除了这些技术问题外，另一个解释为什么精子DNA氧化测量未被纳入男性生育力评估的原因可能是缺乏其在妊娠结局中作用的有力证据。然而，越来越明显的是，DNA碱基氧化的评估可以提高辅助生殖技术的效率，并提供有关胚胎发育失败和后代所患疾病的重要信息。这项工作的目的是综述在精子DNA碱基氧化领域及其相关的遗传和表观遗传后果方面所开展的相关研究。
