Mousavi Seyedeh Zahra, Mohammad-Soltani Bahram, Hadizadeh Morteza, Rokhsattalab Zeynab, Totonchi Mehdi
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Mol Biol Res Commun. 2025;14(4):271-281. doi: 10.22099/mbrc.2025.52777.2123.
Teratozoospermia is an abnormal sperm morphology that is a common cause of male infertility. Epigenetic factors have been implicated in the regulation of gene expression in teratozoospermia, but the specific mechanisms are not fully understood. This study aimed to identify differentially expressed genes (DEGs) between teratozoospermia and normozoospermia samples, and to investigate the role of epigenetic regulatory factors in the observed gene expression changes. The study integrated data from three publicly available datasets in the GSE6969 superseries. The DEGs were compared to a list of known human epigenetic-related genes obtained from the EpiFactors database. The protein-protein interaction (PPI) network and hub gene identifications for Epi-DEGs and the RNA-protein interaction (RPI) network to obtained the RBPs interacting with Epi-DEGs were constructed. siRNA design for the candidate mRNA was performed using various bioinformatics tools. As a result, the obtained 1,292 DEGs were compared to a list of 796 known human epigenetic factors, revealing 63 Epi-DEGs. The PPI network of Epi-DEGs identified top 10 hub genes including , , , , , , , , and . The RPI network analysis revealed , and as key RNA-binding protein regulators epigenetic modifiers. Based on these findings, the study designed the sequence GCAACAAGAGAAGAA GCAATT as an optimal siRNA candidate targeting the master regulator IGF2BP2, which exhibited the most significant change in expression among the RNA-binding proteins (RBPs). This integrative analysis sheds light on the epigenetic mechanisms underlying teratozoospermia and highlights the potential of RBPs as diagnostic biomarkers and therapeutic targets for further investigation.
畸形精子症是一种异常的精子形态，是男性不育的常见原因。表观遗传因素与畸形精子症中基因表达的调控有关，但其具体机制尚未完全明确。本研究旨在鉴定畸形精子症与正常精子症样本之间的差异表达基因（DEGs），并研究表观遗传调控因子在观察到的基因表达变化中的作用。该研究整合了GSE6969超级系列中三个公开可用数据集的数据。将这些DEGs与从EpiFactors数据库获得的已知人类表观遗传相关基因列表进行比较。构建了Epi-DEGs的蛋白质-蛋白质相互作用（PPI）网络和枢纽基因鉴定以及与Epi-DEGs相互作用的RNA结合蛋白（RBPs）的RNA-蛋白质相互作用（RPI）网络。使用各种生物信息学工具对候选mRNA进行siRNA设计。结果，将获得的1292个DEGs与796个已知人类表观遗传因子列表进行比较，发现了63个Epi-DEGs。Epi-DEGs的PPI网络鉴定出前10个枢纽基因，包括 、 、 、 、 、 、 、 、 和 。RPI网络分析显示 、 和 是关键的RNA结合蛋白调节因子表观遗传修饰剂。基于这些发现，该研究设计了序列GCAACAAGAGAAGAA GCAATT作为靶向主要调节因子IGF2BP2的最佳siRNA候选物，IGF2BP2在RNA结合蛋白（RBPs）中表现出最显著的表达变化。这种综合分析揭示了畸形精子症背后的表观遗传机制，并突出了RBPs作为诊断生物标志物和进一步研究的治疗靶点的潜力。
