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中国重庆地区健康男大学生的精子端粒长度与精子核 DNA 完整性和线粒体 DNA 异常有关。

Sperm telomere length is associated with sperm nuclear DNA integrity and mitochondrial DNA abnormalities among healthy male college students in Chongqing, China.

机构信息

Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China.

出版信息

Hum Reprod. 2023 Jun 1;38(6):1036-1046. doi: 10.1093/humrep/dead065.

Abstract

STUDY QUESTION

Is sperm telomere length (STL) associated with sperm nuclear DNA damage and mitochondrial DNA abnormalities?

SUMMARY ANSWER

Sperm telomere length is related to sperm nuclear DNA integrity and mitochondrial DNA abnormalities in healthy young college students.

WHAT IS KNOWN ALREADY

Many studies have revealed the correlations between sperm genetic alterations in both the nucleus and mitochondria and sperm functionality, however, the possible associations between the telomere, an important component of chromosome, and conventional indicators of mitochondrial DNA and nuclear DNA changes have not been investigated.

STUDY DESIGN, SIZE, DURATION: A prospective cohort study, Male Reproductive Health in Chongqing College Students (MARHCS), was conducted from June 2013 to June 2015. We pooled data collected from the follow-up study in 2014 and a total of 444 participants were included.

PARTICIPANTS/MATERIALS, SETTING, METHODS: STL was measured by quantitative (Q)-PCR. Sperm nuclear DNA integrity was determined using sperm chromatin structure assay (SCSA) and comet assay. Mitochondrial DNA damage was assessed by mitochondrial DNA copy number (mtDNAcn) evaluated with Q-PCR, and mtDNA integrity was determined with long PCR.

MAIN RESULTS AND THE ROLE OF CHANCE

The univariable-linear regression analysis revealed that STL was significantly positively correlated with markers of sperm nuclear DNA damage including the DNA fragmentation index (DFI) and comet parameters (the percentage of DNA in the tail, tail length, comet length, and tail moment). Additionally, STL was also significantly positively correlated with mtDNAcn and significantly negatively correlated with mtDNA integrity. After adjustment for potential confounders, these relationships remained appreciable. Moreover, we investigated potential effects of biometric factors, including age, parental age at conception, and BMI on STL and found that STL was increased with paternal age at conception.

LIMITATIONS, REASONS FOR CAUTION: A mechanistic explanation of the correlation between STL, sperm nuclear DNA integrity, and mtDNA abnormalities cannot be provided with a cross-sectional study design, so well-designed longitudinal studies are still necessary. In addition, a single semen samples were provided and were not all obtained at the same time point, which may increase the intraindividual bias in this study.

WIDER IMPLICATIONS OF THE FINDINGS

The findings extend the literature including assessment of mitochondrial dysfunction, sperm nuclear DNA damage, and telomere length and provide new insights into the relevance of STL in male reproduction.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (No. 82073590), the National Natural Science Foundation of China (No. 81903363), the National Natural Science Foundation of China (No. 82130097), and the National Key R&D Program of China (2022YFC2702900). The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

精子端粒长度(STL)是否与精子核 DNA 损伤和线粒体 DNA 异常有关?

总结答案

在健康的年轻大学生中,精子端粒长度与精子核 DNA 完整性和线粒体 DNA 异常有关。

已知情况

许多研究表明,核和线粒体中精子遗传改变与精子功能之间存在相关性,然而,端粒(染色体的重要组成部分)与线粒体 DNA 和核 DNA 变化的常规指标之间的可能关联尚未得到研究。

研究设计、大小、持续时间:这是一项前瞻性队列研究,重庆大学生男性生殖健康研究(MARHCS)于 2013 年 6 月至 2015 年 6 月进行。我们汇总了 2014 年随访研究中收集的数据,共有 444 名参与者被纳入。

参与者/材料、地点、方法:通过定量(Q)-PCR 测量 STL。使用精子染色质结构分析(SCSA)和彗星分析来确定精子核 DNA 完整性。通过 Q-PCR 评估线粒体 DNA 拷贝数(mtDNAcn)来评估线粒体 DNA 损伤,并通过长 PCR 来确定 mtDNA 完整性。

主要结果和机会的作用

单变量线性回归分析显示,STL 与精子核 DNA 损伤的标志物显著正相关,包括 DNA 碎片化指数(DFI)和彗星参数(尾部的 DNA 百分比、尾部长度、彗星长度和尾部矩)。此外,STL 还与 mtDNAcn 显著正相关,与 mtDNA 完整性显著负相关。在调整了潜在混杂因素后,这些关系仍然明显。此外,我们还研究了生物统计学因素(包括年龄、父母受孕年龄和 BMI)对 STL 的潜在影响,发现 STL 随父亲的受孕年龄增加而增加。

局限性、谨慎的原因:横断面研究设计无法提供 STL、精子核 DNA 完整性和 mtDNA 异常之间相关性的机制解释,因此仍然需要精心设计的纵向研究。此外,提供的是单次精液样本,并且并非全部是在同一时间点获得的,这可能会增加本研究中的个体内偏差。

研究结果的更广泛意义

这些发现扩展了关于线粒体功能障碍、精子核 DNA 损伤和端粒长度的文献,并为 STL 在男性生殖中的相关性提供了新的见解。

研究资金/利益冲突:本工作得到国家自然科学基金(No. 82073590)、国家自然科学基金(No. 81903363)、国家自然科学基金(No. 82130097)和国家重点研发计划(2022YFC2702900)的支持。作者声明没有利益冲突。

试验注册编号

N/A。

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