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Front. Endocrinol. | doi: 10.3389/fendo.2019.00821

TMT based proteomic analysis of human follicular fluid from overweight/obese and normal-weight patients with polycystic ovary syndrome

Xinyi Zhang1, Xiaoyan Xu1, Pingping Li1, Feifei Zhou1, Lin Kong1,  Jiahui Qiu1, Zhengwei Yuan1 and  Jichun Tan1*
  • 1ShengJing Hospital of China Medical University, China

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 1153 proteins were identified, of which 41 and 19 proteins were differentially expressed in the overweight/obese PCOS group versus the control group, and in the normal-weight PCOS group versus 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.

Keywords: Polycystic ovary syndrome (PCOS), Follicular Fluid, Obesity, Proteomics, Tandem mass tag (TMT)

Received: 09 Jun 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Zhang, Xu, Li, Zhou, Kong, Qiu, Yuan and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Jichun Tan, ShengJing Hospital of China Medical University, Shenyang, 110004, Liaoning Province, China,