A comprehensive investigation of sperm DNA damage and oxidative stress injury in infertile patients with subclinical, normozoospermic, and astheno/oligozoospermic clinical varicocoele

A comprehensive investigation of sperm DNA damage and oxidative stress injury in infertile patients with subclinical, normozoospermic, and astheno/oligozoospermic clinical varicocoele
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对患有亚临床、正常精子症和弱/少精子症临床精索静脉曲张的不孕患者的精子 DNA 损伤和氧化应激损伤进行全面调查。

DOI:
10.1111/andr.12210
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发表时间:
2016-09-01
期刊:
影响因子:
4.5
通讯作者:
Chen, B.
Chen, B.
中科院分区:
医学2区
文献类型:
--
作者:
Ni, K.;Steger, K.;Chen, B.

文献摘要

被引文献

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氧化应激(oxidative stress,OS)是导致精索静脉曲张和不孕的主要原因之一,但其与不孕患者DNA氧化损伤的关系尚不清楚。本研究的目的是全面探讨精子DNA损伤和OS损伤是否与精索静脉曲张的不同问题有关。根据精索静脉曲张诊疗指南,亚临床型(SubVc,n = 15)和正常精子症临床型精索静脉曲张(NCVc,n = 22)的不育患者不适合手术治疗,弱精子症/少精子症临床型精索静脉曲张(AOCVc,n = 51)的不育患者将接受显微外科精索静脉曲张切除术。招募具有已证实生育力的正常精子健康供体(n = 25)作为对照。采用硫代巴比妥酸法和精子染色质结构分析法(SCSA)检测精子脂质过氧化产物丙二醛(MDA)和精子DNA片段化指数(DFI)。结果表明,AOCVc和NCVc能显著升高精子DFI和MDA水平,SubVc除外。精索静脉曲张切除术可明显改善AOCVc患者的精液参数,降低精子DFI和精液MDA水平。然而,非手术NCVc患者可能会遭受严重的精液参数恶化,伴随着异常较高的精子DFI和精液MDA水平,而非手术SubVc患者没有发生差异。妊娠组精子DFI水平明显低于非妊娠组(AOCVc,p < 0.01; NCVc,p < 0.05),最佳临界值为19.73%,而精液MDA水平无差异(p > 0.05)。精子DFI与精子MDA呈显著正相关(Rs = 0.504,p < 0.01),与除正常形态外的其他重要精液参数也呈显著正相关。因此,精子DNA损伤在临床精索静脉曲张,而不是在SubVc,可能与精液活性氧(ROS)在介导这种损害的作用。精索静脉曲张切除术有利于减少OS损伤和精子DFI,精子DNA片段水平低的男性有更多的妊娠机会。
One of the main pathogeneses of varicocoele and infertility is oxidative stress (OS), nevertheless, the oxidative damaged DNA in infertile patients with varicocoele remains poorly clarified. The objective of this study was to comprehensively investigate whether sperm DNA damage and OS injury were related with different issues of varicocoele. According to the varicocoele practice guidelines, surgical treatment was not indicated in the infertile patients with subclinical (SubVc, n = 15) and normozoospermic clinical varicocoele (NCVc, n = 22), the infertile astheno/oligozoospermic patients with clinical varicocoele (AOCVc, n = 51) would receive micro-surgerical varicocoelectomy. Normozoospermic healthy donors with proven fertility (n = 25) were recruited as controls. Thiobarbituric acid and sperm chromatin structure assay (SCSA) methods were preformed to analyze seminal lipid peroxidation product malondialdehyde (MDA) and sperm DNA fragmentation index (DFI). We found that AOCVc and NCVc, except SubVc, could significantly elevate sperm DFI and seminal MDA levels. Varicocoelectomy could substantially improve semen parameters, and reduce sperm DFI and seminal MDA levels in the AOCVc patients. However, the non-operative NCVc patients would possibly suffer a severe deterioration of semen parameters accompanied by aberrantly higher levels of sperm DFI and seminal MDA, whereas no differences occurred in the non-operative SubVc patients. Sperm DFI level in the pregnant group was much lower compared to the non-pregnant group (AOCVc, p < 0.01; NCVc, p < 0.05) with the best cutoff value of 19.73%, while no differences in seminal MDA (p > 0.05) could be observed. Finally, a strong positive correlation was found between sperm DFI and seminal MDA (Rs = 0.504, p < 0.01), and they were also closely correlated with crucial semen parameters except normal morphology. Therefore, sperm DNA damage in clinical varicocoele, but not in SubVc, might be associated with the role of seminal reactive oxygen species (ROS) in mediating such damage. Varicocoelectomy could be beneficial for reducing OS injury and sperm DFI, and males with low sperm fragmented-DNA level had more opportunities to become pregnant.