关键词: DNA repair Double strand DNA breaks Sperm DNA Testicular sperm

Mesh : Pregnancy Female Humans Male DNA Breaks, Double-Stranded Semen Spermatozoa DNA Repair / genetics Embryo Implantation / genetics

来  源:   DOI:10.1007/s10815-023-02748-5   PDF(Pubmed)

Abstract:
OBJECTIVE: The main objective of this opinion paper was to bring to light and enhance our understanding of the amount of double-strand DNA breaks in sperm and whether there is a threshold of no return when considering repair by the oocyte/embryo.
METHODS: A brief review of literature related to the theories proposed for the appearance of double-strand breaks in human spermatozoa. Further commentary regarding their detection, how oocytes or embryos may deal with them, and what are the consequences if they are not repaired. Finally, a strategy for dealing with patients who have higher levels of double-strand DNA breaks in sperm is proposed by reviewing and presenting data using testicular extracted sperm.
RESULTS: We propose a theory that a threshold may exist in the oocyte that allows either complete or partial DNA repair of impaired sperm. The closer that an embryo is exposed to the threshold, the more the effect on the ensuing embryo will fail to reach various milestones, including blastocyst stage, implantation, pregnancy loss, an adverse delivery outcome, or offspring health. We also present a summary of the role that testicular sperm extraction may play in improving outcomes for couples in which the male has a high double-strand DNA break level in his sperm.
CONCLUSIONS: Double-strand DNA breaks in sperm provide a greater stress on repair mechanisms and challenge the threshold of repair in oocytes. It is therefore imperative that we improve our understanding and diagnostic ability of sperm DNA, and in particular, how double-strand DNA breaks originate and how an oocyte or embryo is able to deal with them.
摘要:
目的:这篇论文的主要目的是揭示并增强我们对精子中双链DNA断裂量的理解,以及在考虑卵母细胞/胚胎修复时是否存在无法返回的阈值。
方法:对与人类精子双链断裂出现的理论有关的文献进行简要回顾。关于他们被发现的进一步评论,卵母细胞或胚胎如何处理它们,如果不修理会有什么后果。最后,通过审查和提供使用睾丸提取的精子的数据,提出了一种处理精子中双链DNA断裂水平较高的患者的策略。
结果:我们提出了一种理论,即卵母细胞中可能存在一个阈值,该阈值允许受损精子的完全或部分DNA修复。胚胎越接近阈值,对随后的胚胎的影响就越无法达到各种里程碑,包括囊胚期,植入,怀孕失败,不良的交付结果,或后代健康。我们还总结了睾丸精子提取在改善男性精子中双链DNA断裂水平较高的夫妇的结局中可能发挥的作用。
结论:精子中的双链DNA断裂对修复机制提供了更大的压力,并挑战了卵母细胞的修复阈值。因此,我们必须提高对精子DNA的理解和诊断能力,特别是,双链DNA断裂的起源以及卵母细胞或胚胎如何处理它们。
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