PLK2 as a key regulator of glycolysis and immune dysregulation in polycystic ovary syndrome

Background Polycystic ovary syndrome (PCOS) is a highly heterogeneous endocrine-metabolic disorder. Ovarian stromal cells influence follicular development and ovulation by secreting cytokines. Glycolysis, a central pathway of glucose metabolism, plays a crucial role in the pathogenesis of PCOS. However, the precise mechanisms underlying dysregulated glycolysis in ovarian stromal cells in PCOS remain unclear. Methods Seurat and CellChat were employed to analyze single-cell RNA sequencing (scRNA-seq) data, incorporating glycolysis scoring and cell-cell communication analysis. Three independent bulk RNA-seq datasets were integrated to identify key genes. Immune infiltration was assessed using CIBERSORT, ESTIMATE, and ssGSEA algorithms. Functional enrichment analysis (GO, KEGG, and Hallmark) was performed to annotate PLK2-related pathways. Finally, a dehydroepiandrosterone (DHEA)-induced PCOS rat model was constructed to validate the critical role of PLK2 expression in PCOS. Results Single-cell sequencing analysis revealed that endothelial cells in the ovarian stroma of PCOS exhibited the highest glycolytic activity and increased intercellular communication, particularly interacting with fibroblasts via the PPIA-BSG ligand-receptor pair. Integrated transcriptomic analysis identified PLK2 as a central regulatory gene of endothelial glycolysis (AUC > 0.85). Functional enrichment analysis further demonstrated that high PLK2 expression was closely associated with extracellular matrix (ECM) remodeling and promoted chronic inflammation and ovarian fibrosis by activating the NF-κB and IL-17 signaling pathways. Immune infiltration analysis indicated that PCOS patients with high PLK2 expression exhibited enhanced pro-inflammatory responses, increased neutrophil recruitment, and impaired T-cell function, suggesting a shift toward an inflammatory ovarian microenvironment. The DHEA-induced PCOS rat model further confirmed the critical role of PLK2 in disease progression and glycolytic dysregulation. Conclusion This study establishes PLK2 as a key regulator of glycolysis and immune imbalance in PCOS, highlighting its pivotal role in the metabolic-immune crosstalk within the ovarian microenvironment. These findings suggest that targeting PLK2 may be a potential therapeutic strategy for alleviating glycolytic dysregulation and chronic inflammation in PCOS.