Proteomics of follicular fluid from women with polycystic ovary syndrome suggests molecular defects in follicular development

Context: Polycystic ovary syndrome (PCOS), a major cause of anovulatory infertility, is characterized by arrested follicular growth. Altered protein levels in the follicular fluid surrounding the ovum may reflect the molecular defects of folliculogenesis in these women. Objective: To identify differentially regulated proteins in PCOS by comparing the follicular fluid protein repertoire of PCOS with healthy women. Methods: The follicular fluid samples were collected from PCOS and normo-ovulatory women undergoing in vitro fertilization. Follicular fluid proteins were subjected to digestion using trypsin, and resultant peptides were labeled with isobarictags for relative and absolute quantification reagents and analyzed by liquid chromatography tandem mass spectrometry. Differential abundance of selected proteins was confirmed by ELISA. Results: A total of 770 proteins were identified, of which 186 showed differential abundance between controls and women with PCOS. Proteins involved in various processes of follicular development including amphiregulin; heparan sulfate proteoglycan 2; tumor necrosis factor, α-induced protein 6; plasminogen; and lymphaticvessel endothelial hyaluronan receptor 1 werefound to be deregulated in PCOS. We also identified a number of new proteins from follicular fluid, whose function in the ovary is not yet clearly established. These include suprabasin; S100 calcium binding protein A7; and helicase with zinc finger 2, transcriptional coactivator. Conclusions: Proteins indispensable for follicular growth were found to be differentially expressed in follicular fluid of women with PCOS, which may in part explain the aberrant folliculogenesis observed in these women.