Journal of Advances in Medical and Biomedical Research

en Transcriptomic Changes in Patients with Severely Impaired Spermatogenesis: A Systems Biology Study Medical Biology Medical Biology مقاله پژوهشی Original Research Article Background & Objective: Male infertility is a common condition, affecting approximately 7% of men worldwide. Spermatogenesis, the production of mature sperm cells, is tightly regulated by several genes and, dysregulation of these genes can impair normal spermatogenesis. This study aimed to identify key genes involved in the regulation of spermatogenesis.  Materials & Methods: We extracted transcriptomic data from testicular samples of patients with impaired spermatogenesis and normal controls (GSE145467, 10 patients and 10 control) from the GEO database. A protein–protein interaction network (PPIN) was constructed using the STRING database and visualized with Cytoscape v3.10.1. Network clusters were identified using the MCODE plugin. In addition, an lncRNA–miRNA–gene regulatory network was constructed, and key genes were identified using Cytoscape software. Finally, Gene Ontology (GO) analysis of the key genes was performed using the DAVID and TAM 2.0 servers. Results:  CDK1, KIF11, AURKA, TEKT1, TUBB4B, CDC25C, ENKUR, CALM3, CCDC39, TYMS, PRKACB, PRKACG, FAM166C, TMEM249, GTF2A2, NRAV lncRNA, miR-1, miR-9, and miR-27b were identified as novel crucial genes in the PPIN and gene regulatory network (GRN). Functional and pathway enrichment analysis revealed that these genes are involved in gap junction communication, long-term potentiation, GnRH signaling, motor protein function, basal transcription factor activity, cell cycle regulation, inflammation, apoptosis, hormone-mediated signaling, and tumor suppressor miRNA pathways. Conclusion:  This multi-layered systems biology analysis identified key genes and pathways associated with spermatogenic failure. Further experimental validation is needed to confirm these findings and evaluate their potential as therapeutic targets. Infertility, Spermatogenesis, Systems Biology, Transcriptome 273 283 http://journal.zums.ac.ir/browse.php?a_code=A-10-6761-2&slc_lang=en&sid=1 Fatemeh Saberi fatemeh.saberi82@gmail.com 0009-0007-1659-5992 No Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zeinab Dehghan dehghan.m.zeinab@gmail.com 0000-0003-4787-1287 No Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran Nasser Gholijani ngholijani@gmail.com 0000-0002-8040-3189 No Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Shayesteh Mehdinejadiani Mehdinejadiani@gmail.com 0000-0002-7905-8314 No Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada Zahra Taheri z.biology87@gmail.com No Department of Biology and Biotechnology, University of Pavia, Pavia, Italy Javad Moayedi javad.moayedi88@gmail.com No Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran Sara Mortezaali Mortezaali.s@gmail.com 0000-0001-8922-9394 No Department of Biotechnology, Biological Faculty, Alzahra University, Tehran, Iran Hakimeh Zali HakimehZali@gmail.com 0000-0003-2770-5759 Yes Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran