Screening and identification of critical Genes and Pathways Associated with Oxidative Stress in non-obstructive azoospermia patients: an integrative bioinformatics study

Abstract

Abstract Azoospermia affects nearly 1% of the entire male population, and 60% of these cases are included as non-obstructive azoospermia (NOA). For a long time, oxidative stress has been considered a controversial factor in the etiology of infertility types, including male azoospermia. In various studies, the role of reactive oxygen species, as a double-edged sword, in the normal function of sperm cells and of course in DNA damage and sperm dysfunction has been reported. However, genes related to the oxidative stress process, which are responsible for infertility disorders in men, have not been specifically investigated. In this study, the expression profile of oxidative stress genes in non-obstructive azoospermia patients was investigated, and dysregulated and differentially expressed genes were obtained using Gene Expression Omnibus (GEO) datasets. Besides the limma package, other packages and tools were used for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network of the mentioned genes. Finally, Hub genes were identified using Cytoscape and CytoHubba plug-in. Finally, 75 differentially expressed oxidative stress-related genes were identified between azoospermic and control groups. These genes were enriched in the functions and pathways related to different cellular stress and oxidative stress. As far as we know, this is the first time the key genes of oxidative stress affecting non-obstructive azoospermia have been investigated. The present study suggests the hub genes JUN, FOS, ATF3, DUSP1, MYC, and HSPA5 as possible potential biomarkers in NOA. It is hoped that our results will shed light on the dark aspects of the association between oxidative stress and azoospermia and that these findings will be used as potential therapeutic and research targets.