Heidary Zohreh, Zaki-Dizaji Majid, Saliminejad Kioomars, Edalatkhah Haleh, Khorram Khorshid Hamid Reza
Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.
Andrologia. 2020 Apr;52(3):e13539. doi: 10.1111/and.13539. Epub 2020 Feb 6.
Asthenozoospermia (AZS), which characterised by reduced forward sperm motility, is a common cause of male infertility. Recently, mitochondrial dysfunction reported in AZS men came to attention for finding the molecular aetiology of AZS. Mitochondria-related microRNAs (miRNAs) are the most important regulators of mitochondrial function through post-transcriptionally modulation of gene expression. Therefore, this study aims to evaluate the expression of four recently reported mitochondrial-related miRNAs (miR-4485-3p/4484/4461 and 4463) in the sperm sample of asthenozoospermic men. RNA was extracted from spermatozoa of 74 volunteers (39 patients with idiopathic AZS and 35 controls with normal fertility), and relative gene expression analysis was performed by quantitative PCR. We used SNORD48 as a normaliser gene, and quantification was calculated by 2 method. The expression of miR-4484 and miR-4461 was not detected in the spermatozoa of cases and controls. However, miR-4485-3p (p = .006) was significantly downregulated in the AZS men compared with the controls, but the miR-4463 expression was not significantly different between the two groups (p = .5). Bioinformatic analysis identified three target genes for miR-4485-3p (DNAH1, KIT and PARK7) that are related to male infertility. In conclusion, the downregulation of miR-4485-3p was associated with idiopathic AZS, which could be a molecular link between mitochondrial dysfunction and AZS.
弱精子症(AZS)以精子前向运动能力降低为特征,是男性不育的常见原因。最近,AZS男性中报道的线粒体功能障碍因寻找AZS的分子病因而受到关注。线粒体相关的微小RNA(miRNA)是通过基因表达的转录后调控来调节线粒体功能的最重要调节因子。因此,本研究旨在评估最近报道的四种线粒体相关miRNA(miR-4485-3p/4484/4461和4463)在弱精子症男性精子样本中的表达。从74名志愿者(39例特发性AZS患者和35例生育能力正常的对照)的精子中提取RNA,并通过定量PCR进行相对基因表达分析。我们使用SNORD48作为标准化基因,并通过2−ΔΔCt方法计算定量。在病例组和对照组的精子中均未检测到miR-4484和miR-4461的表达。然而,与对照组相比,AZS男性中miR-4485-3p(p = 0.006)显著下调,但两组之间miR-4463的表达无显著差异(p = 0.5)。生物信息学分析确定了miR-4485-3p的三个靶基因(DNAH1、KIT和PARK7),它们与男性不育有关。总之,miR-4485-3p的下调与特发性AZS相关,这可能是线粒体功能障碍和AZS之间的分子联系。