Abstract / Summary
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that significantly impacts female fertility. The follicular microenvironment, particularly follicular fluid (FF), plays a critical role in oocyte development, yet the systemic metabolic dysregulation within this niche remains incompletely understood. This study aimed to comprehensively characterize the metabolic and lipidomic profiles of FF in PCOS patients to elucidate underlying mechanisms and identify potential biomarkers. We performed an integrated analysis combining non-targeted metabolomics and targeted lipidomics on FF samples collected from 30 PCOS patients and 30 age-matched non-PCOS controls. Differential metabolites and lipids were identified using multivariate and univariate statistical analyses. Functional enrichment, correlation with clinical parameters, logistic regression, and receiver operating characteristic (ROC) analyses were conducted to evaluate the biological relevance and diagnostic potential of the identified molecules. A total of 603 differential metabolites and 120 differential lipids were identified. Lipid and lipid-like molecules constituted the predominant class of altered metabolites, with widespread downregulation of lysophospholipids and glycerophospholipids, alongside selective accumulation of long-chain triglycerides. Key metabolic perturbations included elevated branched-chain amino acids (D-leucine, L-valine), altered steroid hormone metabolites (reduced progesterone, elevated 17α-estradiol), and significant depletion of tetrahydropteridine, cytosine, and uridine. Targeted lipidomics revealed a characteristic “triglyceride accumulation and phospholipid depletion” pattern, with structural selectivity based on carbon chain length and unsaturation degree. Integrated analysis highlighted glycerophospholipid metabolism, steroid hormone biosynthesis, and insulin resistance pathways as core dysregulated networks. This study provides a comprehensive map of systemic metabolic dysregulation in the PCOS follicular microenvironment, revealing that extensive lipid depletion—particularly of membrane phospholipids—alongside selective triglyceride accumulation, BCAA excess, one-carbon metabolism impairment, and steroid hormone imbalance jointly contribute to compromised oocyte quality. These findings offer novel insights into PCOS pathophysiology and present promising multi-marker panels for clinical auxiliary diagnosis.