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. We identified mitochondrial dysfunction-related hub genes by analyzing three testis transcriptome datasets, and further confirmed their diagnostic value, differential expression in clinical specimens, and immune infiltration associations. For GSE108886 and GSE145467, 35 mitochondrial dysfunction-related differentially expressed genes (MD-DEGs, 10 upregulated and 25 downregulated) were obtained. And 6 common hub genes (COX7A1, COX7A2, COX7B2, MRPS15, AURKAIP1, and PDHA2) were identified. hsa-miR-12,116, hsa-miR-296-5p, and transcription factors (FOXA1, FOXC1, GATA2, SRF) simultaneously targeted two hub MD-DEGs. Diagnostic model incorporating COX7A1, COX7A2, AURKAIP1 and MRPS15 presented preliminary diagnostic efficacy with AUC value of 0.930 (95% CI [0.835-1.000]). Subsequently, RT-qPCR confirmed upregulation of COX7A1 (P < 0.05) and downregulation of COX7A2, COX7B2, MRPS15, AURKAIP1 and PDHA2 (P < 0.05 for all) in NOA patients. In addition, T cells CD8 and Mast cells resting were enriched in NOA patients. MD-DEGs including COX7A1, COX7A2, MRPS15 and AURKAIP1 may play pivotal roles in NOA pathogenesis, and could serve as a pre-biopsy screening tool to stratify patients and monitor therapeutic responses for NOA.