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.

Khan Gulafshana Hafeez, Galazis Nicolas, Docheva Nikolina, Layfield Robert, Atiomo William

Division of Human Development, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre, D Floor, East Block, Nottingham, UK gulafshanahafeez@hotmail.com.| Division of Human Development, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre, D Floor, East Block, Nottingham, UK.| Division of Human Development, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre, D Floor, East Block, Nottingham, UK.| School of Life Sciences, University of Nottingham, Nottingham, UK.| Division of Human Development, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre, D Floor, East Block, Nottingham, UK.

Hum Reprod. 2015 Jan;30(1):133-48. doi: 10.1093/humrep/deu268. Epub 2014 Oct 28.

STUDY QUESTION: Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER: Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. WHAT IS KNOWN ALREADY: Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. STUDY DESIGN, SIZE, DURATION: A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. PARTICIPANTS/MATERIALS, SETTING,
METHODS: In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. MAIN RESULTS AND THE ROLE OF CHANCE: Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen alpha, beta and gamma chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. LIMITATIONS, REASONS FOR CAUTION: The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. WIDER IMPLICATIONS OF THE FINDINGS: This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen alpha, beta and gamma chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital. STUDY FUNDING/COMPETING INTERESTS: No financial support was obtained for this project. There are no conflicts of interest.

Galazis Nicolas, Olaleye Olalekan, Haoula Zeina, Layfield Robert, Atiomo William

Division of Human Development, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre Campus, Nottingham University Hospitals, Nottingham, United Kingdom. ngalazis@gmail.com

Fertil Steril. 2012 Dec;98(6):1590-601.e1. doi: 10.1016/j.fertnstert.2012.08.002.

OBJECTIVE: To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). DESIGN: Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. SETTING: Academic department of obstetrics and gynecology in the United Kingdom. PATIENT(S): A total of 180 women identified in the six studies. INTERVENTION(S): Tissue samples from women with OC vs. tissue samples from women without OC. MAIN OUTCOME MEASURE(S): Proteomic biomarkers, proteomic technique used, and methodologic quality score. RESULT(S): A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-gamma, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. CONCLUSION(S): These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC.

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.