{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:12Z","timestamp":1792800012013,"version":"4.5.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 &amp;gt; 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-\u03baB 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1610713","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T05:25:01Z","timestamp":1757568301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["PLK2 as a key regulator of glycolysis and immune dysregulation in polycystic ovary syndrome"],"prefix":"10.3389","volume":"16","author":[{"given":"Hua","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahe","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongting","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingling","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.07.025","article-title":"Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"120","author":"Teede","year":"2023","journal-title":"Fertil Steril"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-8-41","article-title":"Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan","volume":"8","author":"Teede","year":"2010","journal-title":"BMC Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoad002","article-title":"Eshre guideline: recurrent pregnancy loss: an update in 2022","volume":"2023","author":"Bender Atik","year":"2023","journal-title":"Hum Reprod Open"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-024-01057-w","article-title":"Polycystic ovary syndrome as a metabolic disease","volume":"21","author":"Helvaci","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmh011","article-title":"Macrophage contributions to ovarian function","volume":"10","author":"Wu","year":"2004","journal-title":"Hum Reprod Update"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/00006254-197203000-00016","article-title":"Specific stroma in the cortex and medulla of the ovary. 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