Exploring biomarkers of mitochondrial dynamics in polycystic ovary syndrome and the effect of mesenchymal stem cell transplantation on ovarian mitochondria

Polycystic ovary syndrome (PCOS) is a prevalent gynecological disorder commonly associated with endocrine, reproductive, and metabolic dysfunctions. Mitochondrial dynamics (MD) is essential for cellular homeostasis and is implicated in various metabolic disorders. However, its role in PCOS pathogenesis remains underexplored. Mesenchymal stem cells (MSCs) have shown significant promise in ovarian function restoration. Eight differentially expressed mitochondrial dynamics-related genes (DE-MDRGs) were identified through analysis of PCOS transcriptomic data from public databases. Biomarkers for PCOS were validated based on expression levels. Gene set enrichment analysis (GSEA) was conducted to investigate the functional role of these biomarkers. The expression of these biomarkers was examined across distinct cell clusters in both PCOS and control groups. A PCOS rat model was created, MSCs were transplanted, and the relative expression of the biomarkers was confirmed via RT-qPCR. DDHD2 and MRAS were identified as potential biomarkers, both of which are co-enriched in immune response-related pathways. Granulosa cells (GCs) were categorized into four distinct clusters, with clusters GC2 and GC3 showing higher expression levels in PCOS, while GC1 was more prevalent in the controls. MRAS expression in GC1 was notably lower in PCOS compared to controls. RT-qPCR analysis further revealed that DDHD2 was down-regulated, while MRAS was up-regulated in PCOS. MSC transplantation ameliorated these imbalances. DDHD2 and MRAS are promising novel biomarkers for PCOS, and MSCs appear to protect mitochondrial kinetic homeostasis, offering new insights and potential therapeutic avenues for clinical intervention in PCOS.