Abstract
Background: Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to investigate the follicular fluid proteomic profiles of overweight/obese and normal-weight women with PCOS, to identify novel molecular mechanisms underlying PCOS and to determine the effect of obesity on the follicular fluid protein profiles.Methods: Follicular fluid samples were collected from 3 different groups: overweight/obese PCOS patients (n = 29), normal-weight PCOS patients (n = 29), and normo-ovulatory controls (n = 29). We used a quantitative approach with tandem mass tag labeling and liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins. Differential abundance of four selected proteins was confirmed by ELISA. Gene Set Enrichment Analysis was also conducted to further explore our findings. Furthermore, we compared the clinical, hormonal, and biochemical characteristics of overweight/obese and normal-weight patients with PCOS to determine the effects of obesity.Results: A total of 1,153 proteins were identified, of which 41 and 19 proteins were differentially expressed in the overweight/obese PCOS group vs. the control group, and in the normal-weight PCOS group vs. the control group, respectively. Bioinformatics analyses showed that the inflammatory, immunological, and metabolic-related biological processes were co-enriched in both subgroups of PCOS. Apolipoprotein A-II, complement C5, fetuin-B, and stromal cell-derived factor 1 were found to be involved in various processes and were validated using the ELISA analysis. From clinical features and proteomic data, obesity was found to worsen follicular development disturbances in PCOS.Conclusion: In this proteomic study, a panel of proteins were found differentially expressed in the follicular fluid of PCOS. Inflammatory, immunological, and metabolic abnormalities were identified inside the intra-follicular environment, which could be aggravated by obesity. The identified proteins were correlated with follicular growth and may be considered as candidate biomarkers as well as therapeutic targets of PCOS.
Highlights
Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders with a prevalence ranging from 5 to 10% among women of reproductive age [1, 2]
Impaired oocyte quality and outcomes of in-vitro fertilization (IVF) in PCOS have been linked to changes in the components of Follicular fluid (FF), yet the mechanisms have not been fully elucidated [7, 10]
41 proteins were differentially expressed between Po vs. control groups (Po/C), and 19 were differentially expressed between Pn vs. control groups (Pn/C)
Summary
Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders with a prevalence ranging from 5 to 10% among women of reproductive age [1, 2]. Follicular fluid (FF) serves as the complex microenvironment for oocyte growth, follicular maturation, and germ cell-somatic cell communications [4, 5]. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to investigate the follicular fluid proteomic profiles of overweight/obese and normal-weight women with PCOS, to identify novel molecular mechanisms underlying PCOS and to determine the effect of obesity on the follicular fluid protein profiles
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