Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece.
Embryolab IVF Unit, St. 173-175 Ethnikis Antistaseos, Kalamaria, 55134 Thessaloniki, Greece.
Genes (Basel). 2024 Oct 29;15(11):1393. doi: 10.3390/genes15111393.
BACKGROUND/OBJECTIVES: Male infertility is a complex condition with various underlying genetic factors. microRNAs (miRNAs) play a crucial role in gene regulation, and their disruption can significantly impact fertility. This study aimed to identify variants within miRNA genes and elucidate their impact on male infertility.
Whole genome sequencing was performed on blood samples from men with asthenozoospermia, oligozoospermia, and teratozoospermia, compared to normozoospermic controls. The analysis revealed a significant number of unique variants in each infertile group. We subsequently focused on variants in miRNA regions, followed by an in silico analysis to investigate the role of the identified variants and miRNAs in male infertility.
Focused analysis on miRNA genes identified 19 exclusive variants in teratozoospermic men, 24 in asthenozoospermic, and 27 in oligozoospermic, all mapping to pre-miRNAs or mature miRNAs. Functional analyses using Gene Ontology (GO) and KEGG pathways highlighted key biological processes and pathways disrupted by these variants and miRNA-mRNA interactions, including transcription regulation, signaling, and cancer-related pathways. Furthermore, six variants (rs17797090, rs1844035, rs7210937, rs451887, rs12233076, and rs6787734) were common across the infertile groups, suggesting their importance in male infertility or their potential as biomarkers. Common variants were also validated in another clinically relevant group of men. Some miRNAs with identified variants, such as hsa-miR-449b and hsa-miR-296, have been previously implicated in male infertility and exhibit differential expression between fertile and infertile men, according to the literature, too.
These results provide new insights into the genetic basis of male infertility and open avenues for future research and therapeutic interventions.
背景/目的：男性不育是一种复杂的病症，存在多种潜在的遗传因素。微小 RNA（miRNA）在基因调控中发挥着关键作用，其功能障碍会对生育能力产生重大影响。本研究旨在鉴定 miRNA 基因中的变异，并阐明其对男性不育的影响。
对患有严重少精子症、少精子症和畸形精子症的男性以及正常精子症对照者的血液样本进行全基因组测序。分析显示，每个不育组都存在大量独特的变异。随后，我们专注于 miRNA 区域的变异，并进行了计算机分析，以研究所鉴定的变异和 miRNA 在男性不育中的作用。
对 miRNA 基因的重点分析鉴定了特发性少精子症男性中 19 个独特的变异，严重少精子症男性中 24 个，少精子症男性中 27 个，这些变异均位于前体 miRNA 或成熟 miRNA 上。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行的功能分析突出了这些变异和 miRNA-mRNA 相互作用破坏的关键生物学过程和通路，包括转录调控、信号转导和癌症相关通路。此外，六个变异（rs17797090、rs1844035、rs7210937、rs451887、rs12233076 和 rs6787734）在所有不育组中都很常见，表明它们在男性不育中的重要性或作为生物标志物的潜力。常见变异也在另一组具有临床相关性的男性中得到了验证。一些具有鉴定变异的 miRNA，如 hsa-miR-449b 和 hsa-miR-296，根据文献报道，也与男性不育有关，并且在生育能力正常和不育男性之间存在差异表达。
这些结果为男性不育的遗传基础提供了新的见解，并为未来的研究和治疗干预开辟了新的途径。
