In silico exploring of the epigenetic factors in teratozoospermia: A focus on IGF2BP2

Document Type : Original article

Authors

1 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Abstract

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 RBBP7, HDAC2, EZH2, SMARCA5, SUV39H1, CTCF, DNMT1, MORF4L1, ARID4B and KDM5B. The RPI network analysis revealed IGF2BP2, SFPQ and A1CF 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.

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