Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments

Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments
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DOI:
10.1016/j.fertnstert.2012.11.054
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发表时间:
2013-04-01
影响因子:
6.7
通讯作者:
Backes, Christina
Backes, Christina
中科院分区:
医学2区
文献类型:
--
作者:
Abu-Halima, Masood;Hammadeh, Mohamad;Backes, Christina

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目的:研究microRNAs在精子发生正常与受损男性中的表达差异,寻找准确诊断男性不育症的生物标志物。设计:微阵列实时聚合酶链反应(RT-PCR)验证。单位:高校科研及临床机构。患者:选定夫妇的男性伴侣(n = 27),接受辅助生殖技术治疗不孕症。干预:没有。主要结局指标:在正常精子、弱精子和少精子男性中,microRNA表达谱有统计学意义上的显著改变。结果:弱精子雄性中有50个mirna上调,27个mirna下调。在少精子雄性中,与正常精子雄性相比,42个mirna上调,44个mirna下调。在受体工作特征曲线下表现出最大折叠变化和面积的mirna是弱精子男性样本中的miR-34b、miR-122和miR-1973,以及少精子男性样本中的miR-34b、miR-34b*、miR-15b、miR-34c-5p、miR-122、miR-449a、miR-1973、miR-16和miR-19a。此外,对特定mirna(包括miR-141、miR-200a、miR-122、miR-34b、miR-34c-5p和miR-16)进行定量RT-PCR分析,得出的结果与微阵列数据基本一致。结论:我们的研究结果显示,与正常精子的雄性相比,弱精子和少精子的雄性有更多的mirna差异表达。这些数据为miRNA谱分析作为未来男性不育症的诊断工具提供了证据。肥料(R) 2013;99:1249-55。(C) 2013年由美国生殖医学学会出版。)
Objective: To determine whether microRNAs are differentially expressed in men with normal versus impaired spermatogenesis, and to find a biomarker for accurate diagnosis of male infertility.Design: Microarray with real-time polymerase chain reaction (RT-PCR) validation.Setting: University research and clinical institutes.Patient(s): Male partner of selected couples (n = 27) who were undergoing assisted reproduction techniques for infertility treatment.Intervention(s): None.Main Outcome Measure(s): Statistically significantly altered microRNA expression profiles in normozoospermic versus asthenozoospermic and oligoasthenozoospermic men.Result(s): There were 50 miRNAs up-regulated and 27 miRNAs down-regulated in asthenozoospermic males. In oligoasthenozoospermic males, 42 miRNAs were up-regulated and 44 miRNAs down-regulated when compared with normozoospermic males. The miRNAs that exhibited the highest fold changes and area under the receiver operating characteristic curve were miR-34b, miR-122, and miR-1973 in samples from asthenozoospermic men and miR-34b, miR-34b*, miR-15b, miR-34c-5p, miR-122, miR-449a, miR-1973, miR-16, and miR-19a in samples from oligoasthenozoospermic men. Furthermore, quantitative RT-PCR assays on specific miRNAs, including miR-141, miR-200a, miR-122, miR-34b, miR-34c-5p, and miR-16, yielded results that were largely consistent with the microarray data.Conclusion(s): Our results reveal an extended number of miRNAs that were differentially expressed in asthenozoospermic and oligoasthenozoospermic males compared with normozoospermic males. These data provide evidence for analysis of miRNA profiles as a future diagnosing tool for male infertility. (Fertil Steril (R) 2013; 99:1249-55. (C) 2013 by American Society for Reproductive Medicine.)