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我们是否应该检测人类精子中的 DNA 损伤?旧问题的新视角。

Should we be measuring DNA damage in human spermatozoa? New light on an old question.

机构信息

Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW 2308, Australia.

Monash IVF Group Limited, Level 2, 1 Fennell Street, Parramatta, NSW 2151 Australia.

出版信息

Hum Reprod. 2021 Apr 20;36(5):1175-1185. doi: 10.1093/humrep/deab004.

Abstract

Assessments of sperm DNA damage are controversial because of perceived uncertainties over the relationship with pregnancy and the limited range of therapies available should positive results be returned. In this article, we highlight recent data supporting a chain of associations between oxidative stress in the male germ line, DNA damage in spermatozoa, defective DNA repair in the oocyte, the mutational load carried by the resulting embryo and the long-term health trajectory of the offspring. Any condition capable of generating oxidative damage in spermatozoa (age, obesity, smoking, prolonged abstinence, varicocele, chemical exposures, radiation etc.) is capable of influencing offspring health in this manner, creating a range of pathologies in the progeny including neuropsychiatric disorders and cancer. If sperm DNA damage is detected, there are several therapeutic interventions that can be introduced to improve DNA quality prior to the use of these cells in ART. We therefore argue that infertility specialists should be engaged in the diagnosis and remediation of sperm DNA damage as a matter of best practice, in order to minimize the risk of adverse health outcomes in children conceived using ART.

摘要

由于对精子 DNA 损伤与妊娠的关系存在认知上的不确定性,并且如果结果呈阳性,可采用的治疗方法有限,因此对精子 DNA 损伤的评估存在争议。在本文中,我们强调了最近的数据,这些数据支持了一系列关联,即男性生殖细胞中的氧化应激、精子中的 DNA 损伤、卵母细胞中 DNA 修复缺陷、由此产生的胚胎的突变负荷以及后代的长期健康轨迹之间的关联。任何能够在精子中产生氧化损伤的情况(年龄、肥胖、吸烟、长期禁欲、精索静脉曲张、化学暴露、辐射等)都能够以这种方式影响后代的健康,在后代中产生一系列病理,包括神经精神疾病和癌症。如果检测到精子 DNA 损伤,可以采用几种治疗干预措施,在使用这些细胞进行 ART 之前改善 DNA 质量。因此,我们认为,不孕不育专家应该参与精子 DNA 损伤的诊断和修复,这是最佳实践,以尽量减少使用 ART 受孕的儿童出现不良健康结果的风险。

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