Galazis Nicolas, Docheva Nikolina, Nicolaides Kypros H, Atiomo William

Division of Human Development, School of Clinical Sciences, University of Nottingham, Nottingham, United Kingdom. ngalazis@gmail.com

PLoS One. 2013;8(1):e53801. doi: 10.1371/journal.pone.0053801. Epub 2013 Jan 29.

BACKGROUND: Preterm Birth (PTB) is a major cause of neonatal mortality and morbidity. Women with Polycystic Ovary Syndrome (PCOS) are at high risk of PTB. There is a need for research studies to investigate the mechanisms linking PCOS and PTB, to facilitate screening, and develop novel preventative strategies.
OBJECTIVE: To list all the proteomic biomarkers of PTB and integrate this list with the PCOS biomarker database to identify commonly expressed biomarkers of the two conditions. SEARCH STRATEGY: A systematic review of PTB biomarkers and update of PCOS biomarker database. All eligible published studies on proteomic biomarkers for PTB and PCOS identified through various databases were evaluated. SELECTION CRITERIA: For the identification of the relevant studies, the following search terms were used: "proteomics", "proteomic", "preterm birth", "preterm labour", "proteomic biomarker" and "polycystic ovary syndrome". This search was restricted to humans only DATA COLLECTION AND ANALYSIS: A database on proteomic biomarkers for PTB was created while an already existing PCOS biomarker database was updated. The two databases were integrated and biomarkers that were co-expressed in both women with PCOS and PTB were identified and investigated.
RESULTS: A panel of six proteomic biomarkers was similarly differentially expressed in women with PTB and women with PCOS compared to their respective controls (normal age-matched women in the case of PCOS studies and women with term pregnancy in the case of PTB studies). These biomarkers include Pyruvate kinase M1/M2, Vimentin, Fructose bisphosphonate aldolase A, Heat shock protein beta-1, Peroxiredoxin-1 and Transferrin.
CONCLUSIONS: These proteomic biomarkers (Pyruvate kinase M1/M2, Vimentin, Fructose bisphosphonate aldolase A, Heat shock protein beta-1, Peroxiredoxin-1 and Transferrin) can be potentially used to better understand the pathophysiological mechanisms linking PCOS and PTB. This would help to identify subgroups of women with PCOS at risk of PTB and hence the potential of developing preventative strategies.

Ma Xiang, Fan Lu, Meng Yan, Hou Zheng, Mao Yun-Dong, Wang Wei, Ding Wei, Liu Jia-Yin

Laboratory of Reproductive Medicine, Nanjing Medical University, and The Center of Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, People's Republic of China.

Mol Hum Reprod. 2007 Aug;13(8):527-35. doi: 10.1093/molehr/gam036. Epub 2007 Jun

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, affecting 5-10% of females of reproductive age. Currently, little is known about the changes in whole proteins between PCOS and normal ovaries. In the present study, a proteomic approach comprised two-dimensional gel electrophoresis (2DE) analysis and mass spectroscopy was used to identify proteins and examine expression patterns in three PCOS and normal ovaries. One hundred and ten protein spots were separated and showed different intensities between PCOS and normal ovaries. Sixty-nine proteins associated with cellular metabolism and physiological process were identified from 72 spots. Fifty-four proteins were up-regulated in PCOS ovaries and 15 other proteins were up-regulated in normal ovaries. These data demonstrate, for the first time, the complexity in the regulation of ovarian protein expression in human PCOS, and will provide important insight for a better understanding of the pathogenetic mechanisms underlying this clinical disorder.

Gupta Sajal, Ghulmiyyah Jana, Sharma Rakesh, Halabi Jacques, Agarwal Ashok

Center for Reproductive Medicine, Cleveland Clinic Foundation, 10681 Carnegie Avenue, Desk X11, Cleveland, OH 44195, USA.| Center for Reproductive Medicine, Cleveland Clinic Foundation, 10681 Carnegie Avenue, Desk X11, Cleveland, OH 44195, USA.| Center for Reproductive Medicine, Cleveland Clinic Foundation, 10681 Carnegie Avenue, Desk X11, Cleveland, OH 44195, USA.| Center for Reproductive Medicine, Cleveland Clinic Foundation, 10681 Carnegie Avenue, Desk X11, Cleveland, OH 44195, USA.| Center for Reproductive Medicine, Cleveland Clinic Foundation, 10681 Carnegie Avenue, Desk X11, Cleveland, OH 44195, USA.

Biomed Res Int. 2014;2014:916212. doi: 10.1155/2014/916212. Epub 2014 May 12.

Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.

Atiomo W, Khalid S, Parameshweran S, Houda M, Layfield R

Department of Obstetrics and Gynaecology, School of Human Development, University of Nottingham, and Nottingham University Hospitals, Nottingham, UK. william.atiomo@nottingham.ac.uk

BJOG. 2009 Jan;116(2):137-43. doi: 10.1111/j.1471-0528.2008.02041.x.

BACKGROUND: The exact causes of polycystic ovary syndrome (PCOS) are uncertain, and treatment could be improved. Discovery-based approaches like 'proteomics' may result in faster insights into the causes of PCOS and improved treatment.
OBJECTIVES: To identify the number and nature of proteomic biomarkers found in PCOS so far and to identify their diagnostic and therapeutic potential. SEARCH STRATEGY: All published studies on proteomic biomarkers in women with PCOS identified through the MEDLINE (1966-2008), EMBASE (1980-2008) and the ISI web of knowledge (v4.2) databases. SELECTION CRITERIA: The terms 'polycystic ovary syndrome' and 'proteomic', 'proteomics', 'proteomic biomarker' or 'proteomics biomarker' without any limits/restrictions were used. DATA COLLECTION AND ANALYSIS: Original data were abstracted where available and summarised on a separate Microsoft Excel (2007) database for analysis. MAIN
RESULTS: Seventeen articles were identified, of which 6 original papers and 1 review article contained original data. Tissues investigated included serum, omental biopsies, ovarian biopsies, follicular fluid and T lymphocytes. Sample sizes ranged from 3 to 30 women. One hundred and forty-eight biomarkers were identified. The biomarkers were involved in many pathways, for example the regulation of fibrinolysis and thrombosis, insulin resistance, immunity/inflammation and the antioxidant pathway. Eleven groups of biomarkers appeared to be independently validated. The individual sensitivities for the diagnosis of PCOS were reported for 11 named biomarkers and ranged from 57 to 100%. AUTHOR'S
CONCLUSIONS: Proteomic biomarker discovery in PCOS offers great potential. Current challenges include reproducibility and data analysis. The establishment of a PCOS-specific biomarker data bank and international consensus on the framework of systematic reviews in this field are required.