Abstract
INTRODUCTION: Chronic low-grade inflammation drives polycystic ovary syndrome (PCOS)-related metabolic disorders, but the underlying mechanisms remain unclear. Methylglyoxal, a key ovarian metabolite, promotes inflammation when elevated, its role in PCOS-related inflammation remains uncharacterized. OBJECTIVES: This study aimed to identify the role of methylglyoxal in PCOS-related inflammation and its mechanisms of action. METHODS: This study recruited 258 participants from Shengjing Hospital. White blood cells, neutrophils, and lymphocytes were counted. The Olink Target 96 Inflammation Panel and untargeted metabolomics were used to determine the expression levels of inflammatory factors and metabolites. Key metabolites regulating inflammation were investigated via multiomics analysis (transcriptomics, proteomics, and metabolomics) and machine learning. The levels of methylglyoxal and inflammatory molecules were measured via ELISA. Restricted cubic spline, linear/logistic regression, and receiver operating characteristic (ROC) analyses were performed to examine the relationship between methylglyoxal levels and inflammation. RESULTS: Methylglyoxal levels were notably higher in the follicular fluid and serum of PCOS patients, closely linked to inflammation. Even after adjusting for confounding factors, elevated methylglyoxal levels remained an independent risk factor for inflammatory markers in PCOS patients. In PCOS, insulin resistance and dyslipidemia are associated with increased methylglyoxal concentrations and a more pronounced relationship between methylglyoxal and inflammatory processes. Compared with individuals with normal weight and low methylglyoxal levels, those who were obese or overweight and had high levels of methylglyoxal showed severe inflammatory responses. Additionally, multiomics analysis indicated that IL-17A may serve as a key downstream factor of methylglyoxal. CONCLUSION: We observed significantly elevated methylglyoxal levels in both the follicular fluid and serum of PCOS patients, which were strongly associated with inflammation. Serum methylglyoxal shows promise as a novel biomarker for PCOS-related metabolic-inflammatory dysregulation and may provide a novel target for the treatment of PCOS.