Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biology and Anatomical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Reprod Sci. 2024 Oct;31(10):3112-3121. doi: 10.1007/s43032-024-01640-6. Epub 2024 Jul 16.
The molecular mechanism responsible for sperm DNA fragmentation is not fully understood. Therefore, identifying genes related to the response to DNA damage is an important area of research. Recently, the role of long non-coding RNAs (LncRNAs), especially DNA damage-sensitive RNA1 (DDSR1) in male infertility has been highlighted. In this research, a protein-protein interaction network (PPIN) was constructed using the STRING database, and functional classification was conducted using webgestalt servers. Subsequently, a group of 40 males with a high degree of sperm DNA fragmentation (DFI ≥ 25%) was compared to a control group of 20 healthy males with a normal sperm DNA fragmentation rate (DFI < 25%). To assess gene expression, real-time polymerase chain reaction (PCR) analysis was performed on DNA samples obtained from both healthy and infertile males. Our findings revealed that infertile men with an abnormal DFI index showed significantly lower expression levels of the long noncoding RNA DDSR1, as well as the genes BRCA1, MRE11A, RAD51, and NBN, compared to the control group. Pathway analysis of the network proteins using Reactome indicated involvement in crucial cellular processes such as the cell cycle, DNA repair, meiosis, reproduction, and extension of telomeres. In conclusion, the downregulation of LncRNA and genes associated with the DNA damage response in males with an abnormal DFI suggests that these factors may contribute to the development of sperm DNA fragmentation and could potentially serve as diagnostic markers for further investigation in therapeutic interventions in the future.
导致精子 DNA 碎片化的确切分子机制尚不完全清楚。因此，鉴定与 DNA 损伤反应相关的基因是一个重要的研究领域。最近，长非编码 RNA（lncRNA），尤其是 DNA 损伤敏感 RNA1（DDSR1）在男性不育中的作用受到了关注。在这项研究中，使用 STRING 数据库构建了蛋白质-蛋白质相互作用网络（PPIN），并使用 webgestalt 服务器进行了功能分类。随后，将一组 40 名精子 DNA 碎片化程度较高（DFI≥25%）的男性与 20 名精子 DNA 碎片化率正常（DFI<25%）的健康男性进行了比较。为了评估基因表达，对健康和不育男性的 DNA 样本进行了实时聚合酶链反应（PCR）分析。我们的研究结果表明，与对照组相比，DFI 异常的不育男性的长非编码 RNA DDSR1 以及 BRCA1、MRE11A、RAD51 和 NBN 等基因的表达水平明显降低。使用 Reactome 对网络蛋白进行通路分析表明，它们参与了细胞周期、DNA 修复、减数分裂、生殖和端粒延伸等关键细胞过程。总之，DFI 异常男性中与 DNA 损伤反应相关的 lncRNA 和基因的下调表明，这些因素可能导致精子 DNA 碎片化的发生，并可能成为未来治疗干预中进一步研究的诊断标志物。
