BACKGROUND DNA damage is a hazard that affects all cells of the body. DNA-damage repair (DDR) mechanisms are in place to repair damage and restore cellular function, as are other damage-induced processes such as apoptosis, autophagy and senescence. The resilience of germ cells and embryos in response to DNA damage is less well studied compared with other cell types. Given that recent studies have described links between embryonic handling techniques and an increased likelihood of disease in post-natal life, an update is needed to summarize the sources of DNA damage in embryos and their capacity to repair it. In addition, numerous recent publications have detailed novel techniques for detecting and repairing DNA damage in embryos. This information is of interest to medical or scientific personnel who wish to obtain undamaged embryos for use in offspring generation by ART. OBJECTIVE AND RATIONALE This review aims to thoroughly discuss sources of DNA damage in male and female gametes and preimplantation embryos. Special consideration is given to current knowledge and limits in DNA damage detection and screening strategies. Finally, obstacles and future perspectives in clinical diagnosis and treatment (repair) of DNA damaged embryos are discussed. SEARCH METHODS Using PubMed and Google Scholar until May 2021, a comprehensive search for peer-reviewed original English-language articles was carried out using keywords relevant to the topic with no limits placed on time. Keywords included ‘DNA damage repair’, ‘gametes’, ‘sperm’, ‘oocyte’, ‘zygote’, ‘blastocyst’ and ‘embryo’. References from retrieved articles were also used to obtain additional articles. Literature on the sources and consequences of DNA damage on germ cells and embryos was also searched. Additional papers cited by primary references were included. Results from our own studies were included where relevant. OUTCOMES DNA damage in gametes and embryos can differ greatly based on the source and severity. This damage affects the development of the embryo and can lead to long-term health effects on offspring. DDR mechanisms can repair damage to a certain extent, but the factors that play a role in this process are numerous and altogether not well characterized. In this review, we describe the multifactorial origin of DNA damage in male and female gametes and in the embryo, and suggest screening strategies for the selection of healthy gametes and embryos. Furthermore, possible therapeutic solutions to decrease the frequency of DNA damaged gametes and embryos and eventually to repair DNA and increase mitochondrial quality in embryos before their implantation is discussed. WIDER IMPLICATIONS Understanding DNA damage in gametes and embryos is essential for the improvement of techniques that could enhance embryo implantation and pregnancy success. While our knowledge about DNA damage factors and regulatory mechanisms in cells has advanced greatly, the number of feasible practical techniques to avoid or repair damaged embryos remains scarce. Our intention is therefore to focus on strategies to obtain embryos with as little DNA damage as possible, which will impact reproductive biology research with particular significance for reproductive clinicians and embryologists.

中文翻译：

---

植入前胚胎和配子中的 DNA 损伤：规范、临床相关性和修复策略

背景技术DNA损伤是一种影响身体所有细胞的危害。DNA 损伤修复 (DDR) 机制可以修复损伤和恢复细胞功能，其他损伤诱导过程如细胞凋亡、自噬和衰老也是如此。与其他细胞类型相比，生殖细胞和胚胎对 DNA 损伤的恢复能力研究较少。鉴于最近的研究已经描述了胚胎处理技术与产后疾病可能性增加之间的联系，因此需要更新以总结胚胎中 DNA 损伤的来源及其修复能力。此外，许多最近的出版物都详细介绍了检测和修复胚胎 DNA 损伤的新技术。这些信息对于希望通过 ART 获得未损坏的胚胎用于后代产生的医学或科学人员很感兴趣。目的和理由 本综述旨在彻底讨论雄性和雌性配子和植入前胚胎中 DNA 损伤的来源。特别考虑了 DNA 损伤检测和筛选策略的当前知识和限制。最后，讨论了 DNA 损伤胚胎临床诊断和治疗（修复）的障碍和未来前景。搜索方法 使用 PubMed 和 Google Scholar 直到 2021 年 5 月，使用与主题相关的关键字对经过同行评审的英文原创文章进行了全面搜索，没有时间限制。关键词包括“DNA损伤修复”、“配子”、“精子”、“卵母细胞”、“合子”、“胚泡”和“胚胎”。检索到的文章中的参考文献也被用来获得额外的文章。还检索了有关生殖细胞和胚胎 DNA 损伤的来源和后果的文献。包括主要参考文献引用的其他论文。我们自己研究的结果包括在相关的地方。结果 配子和胚胎中的 DNA 损伤可能因来源和严重程度而有很大差异。这种损害会影响胚胎的发育，并可能对后代造成长期的健康影响。DDR机制可以在一定程度上修复损伤，但在这个过程中起作用的因素很多，而且总体上没有很好的特征。在这篇综述中，我们描述了雄性和雌性配子和胚胎中 DNA 损伤的多因素起源，并提出了选择健康配子和胚胎的筛选策略。此外，还讨论了降低 DNA 受损配子和胚胎的频率并最终修复 DNA 并提高胚胎植入前线粒体质量的可能治疗方案。更广泛的影响 了解配子和胚胎中的 DNA 损伤对于改进可以提高胚胎植入和妊娠成功率的技术至关重要。虽然我们对细胞中 DNA 损伤因子和调控机制的了解有了很大进步，但避免或修复受损胚胎的可行实用技术的数量仍然很少。因此，我们的目的是专注于获得尽可能少的 DNA 损伤的胚胎的策略，这将影响生殖生物学研究，对生殖临床医生和胚胎学家具有特别重要的意义。讨论了可能的治疗解决方案，以减少 DNA 受损配子和胚胎的频率，并最终修复 DNA 并提高胚胎植入前的线粒体质量。更广泛的影响 了解配子和胚胎中的 DNA 损伤对于改进可以提高胚胎植入和妊娠成功率的技术至关重要。虽然我们对细胞中 DNA 损伤因子和调控机制的了解有了很大进步，但避免或修复受损胚胎的可行实用技术的数量仍然很少。因此，我们的目的是专注于获得尽可能少的 DNA 损伤的胚胎的策略，这将影响生殖生物学研究，对生殖临床医生和胚胎学家具有特别重要的意义。讨论了可能的治疗解决方案，以减少 DNA 受损配子和胚胎的频率，并最终修复 DNA 并提高胚胎植入前的线粒体质量。更广泛的影响 了解配子和胚胎中的 DNA 损伤对于改进可以提高胚胎植入和妊娠成功率的技术至关重要。虽然我们对细胞中 DNA 损伤因子和调控机制的了解有了很大进步，但避免或修复受损胚胎的可行实用技术的数量仍然很少。因此，我们的目的是专注于获得尽可能少的 DNA 损伤的胚胎的策略，这将影响生殖生物学研究，对生殖临床医生和胚胎学家具有特别重要的意义。