Exploring the Interconnections Between Mitochondrial Dysfunction and Polycystic Ovary Syndrome: A Comprehensive Integrated Analysis.

Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and is strongly linked to mitochondrial dysfunction (MD) in reproductive-age women. MD contributes to excessive reactive oxygen species (ROS) accumulation, exacerbating disease progression. This study aimed to identify key MD-related genes (MDRGs) involved in PCOS through bioinformatics analyses and experimental validation. Two PCOS transcriptome datasets (GSE34526 and GSE5850) were analyzed to identify differentially expressed genes (DEGs), which were then intersected with MDRGs to obtain MD-related DEGs (MDDEGs). Functional enrichment (GO, KEGG, GSEA) and protein-protein interaction (PPI) network analyses identified eight hub MDDEGs (MMP9, PPP1 CA, PSMD12, LIFR, PRKAA1, ITGAM, SUCLA2, GPBAR1). A rat PCOS model was established to validate hub gene expression via RT-qPCR, western blotting, and immunohistochemistry. The experimental data confirmed that seven hub genes exhibited consistent expression patterns with GSE34526 (P < 0.05), while only PRKAA1 and LIFR matched GSE5850 findings. Additionally, ROC analysis for the five most significant genes (LIFR, PBK, PRKAA1, RCAN1, MMP9) demonstrated promising diagnostic value (AUC > 0.85). This study highlights the role of MD in shaping the immune microenvironment of PCOS and identifies novel molecular targets for potential therapeutic interventions.