Background and Aims: 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. The aim of this study is to identify key genes involved in the regulation of spermatogenesis.
Methods: We extracted transcriptomic data from testicular samples of patients with impaired spermatogenesis and normal controls (GSE145467, 10 patients and 10control) 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, a 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.