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解析精子 DNA 损伤对人类生殖的分子影响。

Unraveling the Molecular Impact of Sperm DNA Damage on Human Reproduction.

机构信息

American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.

Department of Anatomy, Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.

出版信息

Adv Exp Med Biol. 2022;1358:77-113. doi: 10.1007/978-3-030-89340-8_5.

Abstract

Semen analysis is the cornerstone in the investigation of fertility status of male partner. However, more advanced tests have emerged including the analysis of sperm chromatin integrity and DNA damage as markers of semen quality. This is of particular interest, as preserving the genetic information is essential to achieve a successful reproductive event. Moreover, the presence of unrepaired DNA lesions can affect cellular functions, resulting in the onset of pathological conditions associated with male infertility, and the transmission of diseases to the offspring. Hence, in this chapter, we aim to review the main factors leading to sperm DNA damage, along with the different types of damage which can occur. Furthermore, molecular mechanisms involved in DNA repair during spermatogenesis or after fertilization of the oocyte are described, and the laboratory techniques currently used in diagnostics and research, for the analysis of sperm DNA damage are also presented. Finally, the impact of sperm DNA damage on reproductive outcomes such as fertilization and pregnancy rates will be discussed with a focus on animal and human studies, along with the identification of new markers of sperm chromatin integrity.

摘要

精液分析是评估男性生育能力的基石。然而,更先进的测试方法已经出现,包括精子染色质完整性和 DNA 损伤分析,这些方法可作为精液质量的标志物。这一点尤其重要,因为保护遗传信息对于实现成功的生殖事件至关重要。此外,未修复的 DNA 损伤会影响细胞功能,导致与男性不育相关的病理状况的发生,并将疾病遗传给后代。因此,在本章中,我们旨在回顾导致精子 DNA 损伤的主要因素,以及可能发生的不同类型的损伤。此外,还描述了精子发生过程中或卵母细胞受精后 DNA 修复涉及的分子机制,以及目前用于诊断和研究的分析精子 DNA 损伤的实验室技术。最后,将讨论精子 DNA 损伤对受精率和妊娠率等生殖结果的影响,重点关注动物和人类研究,以及鉴定新的精子染色质完整性标志物。

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