Identification of the Metabolomics Signature of Human Follicular Fluid from PCOS Women with Insulin Resistance
Ran Liu, Shun Bai, Shengxia Zheng, Xinyi Zhu, Yan Zhang, Bo Xu, Weidong Zhao
Abstract
Context. Polycystic ovary syndrome (PCOS) is a gynecological endocrine disease, and approximately 60% of patients with PCOS have different degrees of insulin resistance (IR). The regulatory role of metabolic networks in human follicular fluid (FF) related to IR in PCOS remains unclear. Aims. To explore the effect of IR on the metabolism of PCOS by analyzing the changes in FF metabolites in PCOS patients who are undergoing assisted reproductive technology based on the metabonomic platform of ultraperformance gas chromatography coupled to mass spectrometry (GC/MS). Method. Eight PCOS patients with IR (PCOS-IR) and 8 PCOS patients without IR (PCOS-NIR) were enrolled. All patients received controlled ovarian stimulation by using the gonadotropin-releasing hormone (GnRH) antagonist protocol, and the FF of a single dominant follicle was collected on the day of oocyte retrieval. The metabolite profiles of the FF were determined by GC/MS. Key Results. A total of 20 differentially expressed metabolites in FF were identified. Compared with levels in the PCOS-NIR group, stearic acid, palmitic acid, pentadecanoic acid, stigmasterol, citric acid, isocitric acid, thymine, and pyruvic acid in FF were significantly increased in the PCOS-IR group. Lithocholic acid and sinapinic acid in FF decreased significantly. The affected metabolic pathways with potential regulatory roles were identified by KEGG annotation. Conclusion. Compared with the PCOS-NIR group, the PCOS-IR group showed more significant metabolic abnormalities. Implications. These results will help us to understand the pathogenesis of PCOS combined with IR and will provide new clues for studying metabolic disorders associated with PCOS, e.g., IR.