Proteomics of follicular fluid from women with polycystic ovary syndrome suggests molecular defects in follicular development.
BACKGROUND
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 isobaric tags 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 lymphatic vessel endothelial hyaluronan receptor 1 were found 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.
Department of Molecular Endocrinology (A.S.A., S.M.), National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai 400012, India; Institute of Bioinformatics (D.S.K., S.M.P., A.P., T.S.K.P., H.G.), International Technology Park, Bangalore 560066, India; Manipal University (S.M.P.), Madhav Nagar, Manipal 576104, Karnataka, India; Department of Neurochemistry (R.S.), National Institute of Mental Health and Neuro Sciences, Bangalore 560066, India; INKUS IVF Clinic (I.H., K.Z.), Mumbai 400004, India; and McKusick-Nathans Institute of Genetic Medicine and Departments of Biological Chemistry, Pathology and Oncology (A.P.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Aditi S
AS
Ambekar
Dhanashree S
DS
Kelkar
Sneha M
SM
Pinto
Rakesh
R
Sharma
Indira
I
Hinduja
Kusum
K
Zaveri
Akhilesh
A
Pandey
T S Keshava
TS
Prasad
Harsha
H
Gowda
Srabani
S
Mukherjee
D000328:Adult; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism*; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D040901:Proteomics