Integrative bioinformatics analyses of mitochondrial dysfunction-related genes in human non-obstructive azoospermia

Non-obstructive azoospermia (NOA) is the severest form of male infertility. This study aimed to identify core genes associated with mitochondrial dysfunction and regulatory networks in NOA, providing potential diagnostic biomarkers and therapeutic targets for NOA. Three microarray-based transcriptome datasets (GSE108886, GSE145467, GSE9210) of testis tissue were analyzed. Mitochondrial dysfunction-related differentially expressed genes (MD-DEGs) were screened. Protein-protein interaction network was constructed and hub MD-DEGs were identified. The diagnosis value of hub genes was validated and immune infiltration analysis was performed. Additionally, the differential expression of hub genes were validated in clinical testis specimens. For GSE108886 and GSE145467, 35 MD-DEGs (10 up-regulated and 25 down-regulated) were obtained. And 6 common hub genes (COX7A1, COX7A2, COX7B2, MRPS15, AURKAIP1 and PDHA2) were identified. Diagnostic model incorporating COX7A1, COX7A2, AURKAIP1 and MRPS15 presented high diagnostic efficacy with AUC value of 0.930. Subsequently, RT-qPCR confirmed upregulation of COX7A1 ( P< 0.05) and downregulation of COX7A2, COX7B2, MRPS15, AURKAIP1and PDHA2 ( P< 0.05 for all) in NOA patients. In addition, T cells CD8 and Mast cells resting were determined to be enriched in NOA patients. MD-DEGs including COX7A1, COX7A2, MRPS15 and AURKAIP1 may play pivotal roles in NOA pathogenesis, and serve as promising diagnostic biomarkers and therapeutic targets for NOA.