Abstract: To gain insight into the molecula mechanism of male spermatogenic dysfunction remains. In this study,we aimed to identify potential key pathways that are associated with the development of reproductive disorder through bioinformatic analysis of GEO dataset（GSE4797）. Differential expressed genes（DEGs） were identified using the online software GEO2R. DAVID was applied to characterize the significantly enriched Gene Ontology（GO） categories and KEGG pathways for DEGs. Furthermore, the protein-protein interaction（PPI） network was constructed by STRING and the key modules were screened based on the MCODE analysis. Subsequently, we detected hub genes using CytoHubba plugin. In total, 1 637 DEGs were identified in patients with testicular dysfunction relative to healthy controls, including 636 up-regulated genes and 1 001 down-regulated genes. Through MCODE analysis, we found that DEGs are enriched in protein ubiquitination, immune response and cell cycle. Further CytoHubba analysis indicated that the top 10 Hub genes, including SKP1, FBXO6, FBXO32, FBXO31, etc., are involved in protein ubiquitination, all of which share very high connectivity. In combination with previous reports and the details in this analysis, we proposed for the first time that disorder of protein ubiquitination may be critically involved in male spermatogenic dysfunction, and we believe that ubiquitin-related enzymes might be potential drug targets for treating male infertility.