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Proteomic sift through serum and endometrium profiles unraveled signature proteins associated with subdued fertility and dampened endometrial receptivity in women with polycystic ovary syndrome

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Abstract

The objective of this study is to discern the proteomic differences responsible for hampering the receptivity of endometrium and subduing the fertility of females with polycystic ovary syndrome in analogy to healthy fertile females. This study was designed in collaboration with Hakeem Abdul Hameed Centenary Hospital affiliated to Jamia Hamdard, New Delhi, India. Serum samples were taken from infertile PCOS subjects (n = 6) and fertile control subjects (n = 6) whereas endometrial tissue samples were recruited from ovulatory PCOS (n = 4), anovulatory PCOS (n = 4) and normal healthy fertile control subjects (n = 4) for proteomic studies. Additionally, endometrial biopsies from healthy fertile control (n = 8), PCOS with infertility (n = 6), unexplained infertility (n = 3) and endometrial hyperplasia (n = 3) were taken for validation studies. Anthropometric, biochemical and hormonal evaluation was done for all the subjects enrolled in this study. Protein profiles were generated through 2D-PAGE and differential proteins analyzed with PD-QUEST software followed by identification with MALDI-TOF MS protein mass fingerprinting. Validation of identified proteins was done through RT-PCR relative expression analysis. Protein profiling of serum revealed differential expression of proteins involved in transcriptional regulation, embryogenesis, DNA repair, decidual cell ploidy, immunomodulation, intracellular trafficking and degradation processes. Proteins involved in cell cycle regulation, cellular transport and signaling, DNA repair, apoptotic processes and mitochondrial metabolism were found to be differentially expressed in endometrium. The findings of this study revealed proteins that hold strong candidature as potential drug targets to regulate the cellular processes implicating infertility and reduced receptivity of endometrium in women with polycystic ovary syndrome.

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References

  1. Ahmad AK, Kao CN, Quinn M, Lenhart N, Rosen M, Cedars MI, Huddleston H (2018) Differential rate in decline in ovarian reserve markers in women with polycystic ovary syndrome compared with control subjects: results of a longitudinal study. Fertil Steril 109:526–531

  2. Amjadi F, Mehdizadeh M, Ashrafi M, Nasrabadi D, Taleahmad S, Mirzaei M, Gupta V, Salekdeh GH, Aflatoonian R (2018) Distinct changes in the proteome profile of endometrial tissues in polycystic ovary syndrome compared with healthy fertile women. Reprod BioMed Online 37:184–200

  3. Anagnostis P, Tarlatzis BC, Kauffman RP (2017) Polycystic ovarian syndrome (PCOS): long-term metabolic consequences. Metabolism

  4. Bagatur Y, Ilter Akulke AZ, Bihorac A, Erdem M, Telci D (2018) Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma. Cell Adhes Migr 12:138–151

  5. Bellver J, Rodriguez-Tabernero L, Robles A, Munoz E, Martinez F, Landeras J, Garcia-Velasco J, Fontes J, Alvarez M, Alvarez C, Acevedo B (2018) Polycystic ovary syndrome throughout a woman’s life. J Assist Reprod Genet 35:25–39

  6. Best A, Dagliesh C, Ehrmann I, Kheirollahi-Kouhestani M, Tyson-Capper A, Elliott DJ (2013) Expression of Tra2 beta in cancer cells as a potential contributory factor to neoplasia and metastasis. International journal of cell biology 2013:843781

  7. Bhagwat SR, Chandrashekar DS, Kakar R, Davuluri S, Bajpai AK, Nayak S, Bhutada S, Acharya K, Sachdeva G (2013) Endometrial receptivity: a revisit to functional genomics studies on human endometrium and creation of HGEx-ERdb. PLoS One 8

  8. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO (2016) The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction (Oxford, England) 31:2841–2855

  9. Bullard RS, Gibson W, Bose SK, Belgrave JK, Eaddy AC, Wright CJ, Hazen-Martin DJ, Lage JM, Keane TE, Ganz TA, Donald CD (2008) Functional analysis of the host defense peptide human beta defensin-1: new insight into its potential role in cancer. Mol Immunol 45:839–848

  10. Burnstock G (2014) Purinergic signalling in the reproductive system in health and disease. Purinergic Signalling 10:157–187

  11. Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, Nix MA, Kerns JA, Schmutz SM, Millhauser GL, Barsh GS (2007) A -defensin mutation causes black coat color in domestic dogs. Science (New York, NY) 318:1418–1423

  12. Cao L, Shao M, Schilder J, Guise T, Mohammad KS, Matei D (2012) Tissue transglutaminase links TGF-beta, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer. Oncogene 31:2521–2534

  13. Cecchino GN, Seli E, Alves da Motta EL, García-Velasco JA (2018) The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights. Reprod BioMed Online 36:686–697

  14. Chaudhari AP, Mazumdar K, Mehta PD (2018) Anxiety, depression, and quality of life in women with polycystic ovarian syndrome. Indian J Psychol Med 40:239–246

  15. Churchill SJ, Wang ET, Pisarska MD (2015) Metabolic consequences of polycystic ovary syndrome. Minerva Ginecol 67:545–555

  16. Cohen MS, Chang P (2018) Insights into the biogenesis, function, and regulation of ADP-ribosylation. Nat Chem Biol 14:236

  17. Collins T, Sander TL (2005) The superfamily of SCAN domain containing zinc finger transcription factors. In: Iuchi S, Kuldell N (eds) Zinc finger proteins: from atomic contact to cellular function. Springer US, Boston, pp 156–167

  18. Conn JJ, Jacobs HS, Conway GS (2000) The prevalence of polycystic ovaries in women with type 2 diabetes mellitus. Clin Endocrinol 52:81–86

  19. De Leo V, Lanzetta D, D’Antona D, La Marca A, Morgante G (1998) Hormonal effects of flutamide in young women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism 83:99–102

  20. Ding K, Li W, Zou Z, Zou X, Wang C (2014) CCNB1 is a prognostic biomarker for ER+ breast cancer. Med Hypotheses 83:359–364

  21. Dong S, Han J, Chen H, Liu T, Huen Michael SY, Yang Y, Guo C, Huang J (2014) The human SRCAP chromatin remodeling complex promotes DNA-end resection. Curr Biol 24:2097–2110

  22. Edelstein LC, Collins T (2005) The SCAN domain family of zinc finger transcription factors. Gene 359:1–17

  23. Fadda A, Syed N, Mackeh R, Papadopoulou A, Suzuki S, Jithesh PV, Kino T (2017) Genome-wide regulatory roles of the C2H2-type zinc finger protein ZNF764 on the glucocorticoid receptor. Sci Rep 7:41598

  24. Fischer DC, Noack K, Runnebaum IB, Watermann DO, Kieback DG, Stamm S, Stickeler E (2004) Expression of splicing factors in human ovarian cancer. Oncol Rep 11:1085–1090

  25. Fisher SA, Mende Y, Wirth B, Fu K (2011) Transformer (Tra2β): master regulator of myosin phosphatase alternative splicing and smooth muscle responses to NO/cGMP signaling. BMC Pharmacol 11:P24

  26. Fruitwala S, El-Naccache DW, Chang TL (2018) Multifaceted immune functions of human defensins and underlying mechanisms. Semin Cell Dev Biol

  27. Fu D, Samson LD (2012) Direct repair of 3,N(4)-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase. DNA repair 11:46–52

  28. Gao Q, Sun LL, Xiang FF, Gao L, Jia Y, Zhang JR, Tao HB, Zhang JJ, Li WJ (2014) Crybb2 deficiency impairs fertility in female mice. Biochem Biophys Res Commun 453:37–42

  29. Gao Q, Ren H, Chen M, Niu Z, Tao H, Jia Y, Zhang J, Li W (2016) Long non-coding RNAs regulate effects of beta-crystallin B2 on mouse ovary development. Mol Med Rep 14:4223–4231

  30. Garcia-Garcia MJ, Shibata M, Anderson KV (2008) Chato, a KRAB zinc-finger protein, regulates convergent extension in the mouse embryo. Development (Cambridge, England) 135:3053–3062

  31. Gonatopoulos-Pournatzis T, Cowling Victoria H (2014) RAM function is dependent on Kapβ2-mediated nuclear entry. Biochem J 457:473–484

  32. Gonatopoulos-Pournatzis T, Dunn S, Bounds R, Cowling Victoria H (2011) RAM/Fam103a1 is required for mRNA cap methylation. Mol Cell 44:585–596

  33. González F (2012) Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77:300–305

  34. Gorodeski GI (2012) P2X7 receptors and epithelial cancers. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 1:349–371

  35. Grigoryan OR, Zhemaite NS, Volevodz NN, Andreeva EN, Melnichenko GA, Dedov II (2017) Long-term consequences of polycystic ovary syndrome. Terapevticheskii arkhiv 89:75–79

  36. Guo F, Liu Y, Li Y, Li G (2010) Inhibition of ADP-ribosylation factor-like 6 interacting protein 1 suppresses proliferation and reduces tumor cell invasion in CaSki human cervical cancer cells. Mol Biol Rep 37:3819–3825

  37. Hillman SC, Dale J (2018) Polycystic ovarian syndrome: an under-recognised problem? The British journal of general practice : the journal of the Royal College of General Practitioners 68:244

  38. Huang T, Chen S, Han H, Li H, Huang Z, Zhang J, Yin Q, Wang X, Ma X, Dai P, Duan D, Zou F, Chen X (2014) Expression of Hsp90alpha and cyclin B1 were related to prognosis of esophageal squamous cell carcinoma and keratin pearl formation. Int J Clin Exp Pathol 7:1544–1552

  39. Huang JY, Wang K, Vermehren-Schmaedick A, Adelman JP, Cohen MS (2016) PARP6 is a regulator of hippocampal dendritic morphogenesis. Sci Rep 6:18512

  40. Hudecova M, Jan H, Christian B, Poromaa Inger S (2012) Long-term reproductive and metabolic consequences of PCOS. Curr Diabetes Rev 8:444–451

  41. Joham AE, Teede HJ, Ranasinha S, Zoungas S, Boyle J (2015) Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J Women's Health 24(2002):299–307

  42. Kabir-Salmani M, Shiokawa S, Akimoto Y, Sakai K, Sakai K, Iwashita M (2005) Tissue transglutaminase at embryo-maternal Interface. The Journal of Clinical Endocrinology & Metabolism 90:4694–4702

  43. Karen T, Perdita EB, Julia RD (2008) Structure–activity relationships in β-defensin peptides. Pept Sci 90:1–7

  44. Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y (2005) A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res 65:5638–5646

  45. Kerr C, Szmacinski H, Fisher ML, Nance B, Lakowicz JR, Akbar A, Keillor JW, Lok Wong T, Godoy-Ruiz R, Toth EA, Weber DJ, Eckert RL (2016) Transamidase site-targeted agents alter the conformation of the transglutaminase cancer stem cell survival protein to reduce GTP binding activity and cancer stem cell survival. Oncogene 36:2981

  46. Klentzeris LD (1997) The role of endometrium in implantation. Human reproduction (Oxford, England) 12:170–175

  47. Koliwer J, Park M, Bauch C, von Zastrow M, Kreienkamp H-J (2015) The Golgi-associated PDZ domain protein PIST/GOPC stabilizes the β1-adrenergic receptor in intracellular compartments after internalization. J Biol Chem

  48. Koppen M, Simske JS, Sims PA, Firestein BL, Hall DH, Radice AD, Rongo C, Hardin JD (2001) Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia. Nat Cell Biol 3:983–991

  49. Lauritsen MP, Bentzen JG, Pinborg A, Loft A, Forman JL, Thuesen LL, Cohen A, Hougaard DM, Nyboe Andersen A (2014) The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Mullerian hormone. Human reproduction (Oxford, England) 29:791–801

  50. Lee J, Condello S, Yakubov B, Emerson R, Caperell-Grant A, Hitomi K, Xie J, Matei D (2015) Tissue transglutaminase mediated tumor-Stroma interaction promotes pancreatic cancer progression. Clinical cancer research : an official journal of the American Association for Cancer Research 21:4482–4493

  51. Levine RF, Derks R, Beaman K (2005) Regeneration and tolerance factor. A vacuolar ATPase with consequences. Chemical immunology and allergy 89:126–134

  52. Li X, Qi X, Zhou L, Catera D, Rote NS, Potashkin J, Abdul-Karim FW, Gorodeski GI (2007) Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells. Gynecol Oncol 106:233–243

  53. Li L, Tao Q, Jin H, Av H, Poon FF, Wang X, M-s Z, Jia W, Zeng Y-X, Chan AT, Cao Y (2010) The tumor suppressor UCHL1 forms a complex with p53/MDM2/ARF to promote p53 signaling, and is frequently silenced in nasopharyngeal carcinoma. Clin Cancer Res

  54. Lin SR, Yu IS, Huang PH, Tsai CW, Lin SW (2000) Chimaeric mice with disruption of the gene coding for phosphatidylinositol glycan class a (pig-a) were defective in embryogenesis and spermatogenesis. Br J Haematol 110:682–693

  55. Liu Y, Yuan Q, Xie L (2018) The AlkB family of Fe (II)/alpha-ketoglutarate-dependent dioxygenases modulates embryogenesis through epigenetic regulation. Current stem cell research & therapy 13:136–143

  56. Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R (2016) Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 106:6–15

  57. Lo Y-W, Lin S-T, Chang S-J, Chan C-H, Lyu KW, Chang J-F, May EWS, Lin D-Y, Chou H-C, Chan H-L (2015) Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer. J Cell Mol Med 19:744–759

  58. Lopes IM, Baracat MC, Simoes Mde J, Simoes RS, Baracat EC, Soares JM Jr (2011) Endometrium in women with polycystic ovary syndrome during the window of implantation. Revista da Associacao Medica Brasileira 57(1992):702–709

  59. Lupo A, Cesaro E, Montano G, Zurlo D, Izzo P, Costanzo P (2013) KRAB-zinc finger proteins: a repressor family displaying multiple biological functions. Current Genomics 14:268–278

  60. Ma X, Gao F, Rusie A, Hemingway J, Ostmann AB, Sroga JM, Jegga AG, Das SK (2011) Decidual cell polyploidization necessitates mitochondrial activity. PLoS One 6:e26774

  61. Mahmoud SA, Zhang L, Jia C, Zang H (2016) Adverse long-term metabolic and endometrial consequences in women with polycystic ovarian syndrome: a report of two cases. The Journal of reproductive medicine 61:302–305

  62. Mittelstadt M, Frump A, Khuu T, Fowlkes V, Handy I, Patel CV, Patel RC (2008) Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR. Nucleic Acids Res 36:998–1008

  63. Mohammadi M (2019) Oxidative stress and polycystic ovary syndrome: a brief review. International journal of preventive medicine 10:86

  64. Nakakido M, Tamura K, Chung S, Ueda K, Fujii R, Kiyotani K, Nakamura Y (2016) Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors. Int J Oncol 49:868–876

  65. Nakao K, Hirakawa T, Suwa H, Kogure K, Ikeda S, Yamashita S, Minegishi T, Kishi H (2018) High expression of ubiquitin C-terminal hydrolase L1 is associated with poor prognosis in endometrial cancer patients. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 28:675–683

  66. Nay SL, Lee DH, Bates SE, O’Connor TR (2012) Alkbh2 protects against lethality and mutation in primary mouse embryonic fibroblasts. DNA repair 11:502–510

  67. Ohara N, Haraguchi N, Koseki J, Nishizawa Y, Kawai K, Takahashi H, Nishimura J, Hata T, Mizushima T, Yamamoto H, Ishii H, Doki Y, Mori M (2017) Low expression of the GOPC is a poor prognostic marker in colorectal cancer. Oncol Lett 14:4483–4490

  68. Palmer ML, Schiller KR, O’Grady SM (2007) Estrogen and progesterone differentially regulate UTP-stimulated anion secretion in endometrial epithelial cells by altering expression of P2Y receptors and basolateral K+ channels. FASEB J 21:A956–A956

  69. Patel RS, Carter G, Cooper DR, Apostolatos H, Patel NA (2014) Transformer 2 beta homolog (drosophila) (TRA2B) regulates protein kinase C deltaI (PKCδI) splice variant expression during 3T3L1 pre-adipocyte cell cycle. J Biol Chem

  70. Pelaseyed T, Hansson GC (2011) CFTR anion channel modulates expression of human transmembrane mucin MUC3 through the PDZ protein GOPC. J Cell Sci

  71. Popovici RM, Betzler NK, Krause MS, Luo M, Jauckus J, Germeyer A, Bloethner S, Schlotterer A, Kumar R, Strowitzki T, von Wolff M (2006) Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. Endocrinology 147:5662–5675

  72. Quenneville S, Turelli P, Bojkowska K, Raclot C, Offner S, Kapopoulou A, Trono D (2012) The KRAB-ZFP/KAP1 system contributes to the early embryonic establishment of site-specific DNA methylation patterns maintained during development. Cell Rep 2:766–773

  73. Ramezani Tehrani F, Montazeri SA, Hosseinpanah F, Cheraghi L, Erfani H, Tohidi M, Azizi F (2015) Trend of cardio-metabolic risk factors in polycystic ovary syndrome: a population-based prospective cohort study. PLoS One 10:e0137609

  74. Ramos SB, Stumpo DJ, Kennington EA, Phillips RS, Bock CB, Ribeiro-Neto F, Blackshear PJ (2004) The CCCH tandem zinc-finger protein Zfp36l2 is crucial for female fertility and early embryonic development. Development (Cambridge, England) 131:4883–4893

  75. Rashid N, Nigam A, Saxena P, Jain SK, Wajid S (2017) Association of IL-1beta, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome. Inflammation research : official journal of the European Histamine Research Society [et al] 66:621–636

  76. Raval MH, Quintero OA, Weck ML, Unrath WC, Gallagher JW, Cui R, Kachar B, Tyska MJ, Yengo CM (2016) Impact of the motor and tail domains of class III myosins on regulating the formation and elongation of actin protrusions. J Biol Chem 291:22781–22792

  77. Roberts JM, Ennajdaoui H, Edmondson C, Wirth B, Sanford JR, Chen B (2014) Splicing factor TRA2B is required for neural progenitor survival. J Comp Neurol 522:372–392

  78. Schulte MM, Tsai JH, Moley KH (2015) Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation. Reproductive sciences (Thousand Oaks, Calif) 22:6–14

  79. Semple CA, Gautier P, Taylor K, Dorin JR (2006) The changing of the guard: molecular diversity and rapid evolution of β-defensins. Mol Divers 10:575–584

  80. Singh M, Chaudhry P, Asselin E (2011) Bridging endometrial receptivity and implantation: network of hormones, cytokines, and growth factors. J Endocrinol 210:5–14

  81. Slater NM, Barden JA, Murphy CR (2000) Distributional changes of purinergic receptor subtypes (P2X 1-7) in uterine epithelial cells during early pregnancy. Histochem J 32:365–372

  82. Sun M, Holter SM, Stepan J, Garrett L, Genius J, Kremmer E, Hrabe de Angelis M, Wurst W, Lie DC, Bally-Cuif L, Eder M, Rujescu D, Graw J (2013) Crybb2 coding for betaB2-crystallin affects sensorimotor gating and hippocampal function. Mammalian genome : official journal of the International Mammalian Genome Society 24:333–348

  83. Tapia A, Gangi LM, Zegers-Hochschild F, Balmaceda J, Pommer R, Trejo L, Pacheco IM, Salvatierra AM, Henríquez S, Quezada M, Vargas M, Ríos M, Munroe DJ, Croxatto HB, Velasquez L (2008) Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy. Hum Reprod 23:340–351

  84. Tolstrup J, Jónsdóttir F, Ring CM, Andersen M, Elers J, Hedengran K, Holm AM, Lauenborg J (2016) Complications in pregnant women with polycystic ovary syndrome. Ugeskrift for laeger. 178 :V05150439- V05150439

  85. Tosi A, Haas C, Herzog F, Gilmozzi A, Berninghausen O, Ungewickell C, Gerhold CB, Lakomek K, Aebersold R, Beckmann R, Hopfner KP (2013) Structure and subunit topology of the INO80 chromatin remodeler and its nucleosome complex. Cell 154:1207–1219

  86. Tu C-T, Yang T-C, Huang H-Y, Tsai H-J (2012) Zebrafish arl6ip1 is required for neural crest development during embryogenesis. PLoS One 7:e32899

  87. Tuncel H, Tanaka S, Oka S, Nakai S, Fukutomi R, Okamoto M, Ota T, Kaneko H, Tatsuka M, Shimamoto F (2012) PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development. Int J Oncol 41:2079–2086

  88. Ummanni R, Jost E, Braig M, Lohmann F, Mundt F, Barett C, Schlomm T, Sauter G, Senff T, Bokemeyer C, Sültmann H, Meyer-Schwesinger C, Brümmendorf TH, Balabanov S (2011) Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) is a potential tumour suppressor in prostate cancer and is frequently silenced by promoter methylation. Mol Cancer 10:129

  89. Wang J, Li Y, Zhang M, Liu Z, Wu C, Yuan H, Li Y-Y, Zhao X, Lu H (2007) A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor rev-erbβ and removes rev-erbβ-induced inhibition of apoCIII transcription. FEBS J 274:5370–5381

  90. Wang IX, Ramrattan G, Cheung VG (2015a) Genetic variation in insulin induced kinase signaling. Molecular systems biology 11:7

  91. Wang Z, Slipicevic A, Forsund M, Trope CG, Nesland JM, Holm R (2015b) Expression of CDK1(Tyr15), pCDK1(Thr161), Cyclin B1 (total) and pCyclin B1(Ser126) in vulvar squamous cell carcinoma and their relations with clinicopatological features and prognosis. PLoS One 10:e0121398

  92. Wang S, Peng Z, Wang S, Yang L, Chen Y, Kong X, Song S, Pei P, Tian C, Yan H, Ding P, Hu W, Liu CH, Zhang X, He F, Zhang L (2018) KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration. Cell Res 28:572–592

  93. Xia H, Zhang R, Sun X, Wang L, Zhang W (2017) Risk factors for preeclampsia in infertile Chinese women with polycystic ovary syndrome: a prospective cohort study. Journal of clinical hypertension (Greenwich, Conn) 19:504–509

  94. Xiang F, Cui B, Gao Q, Zhang J, Zhang J, Li W (2012a) Decreased levels of Ca(2)(+)-calmodulin-dependent protein kinase IV in the testis as a contributing factor to reduced fertility in male Crybb2(−)/(−) mice. Int J Mol Med 30:1145–1151

  95. Xiang T, Li L, Yin X, Yuan C, Tan C, Su X, Xiong L, Putti TC, Oberst M, Kelly K, Ren G, Tao Q (2012b) The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer. PLoS One 7:e29783

  96. Yamamoto Y, Yoshida A, Miyazaki N, Iwasaki K, Sakisaka T (2014) Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-like fashion. The Biochemical journal 458:69–79

  97. Yang Z, Cao Y, Zhu X, Huang Y, Ding Y, Liu X (2009) Znhit1 causes cell cycle arrest and down-regulates CDK6 expression. Biochem Biophys Res Commun 386:146–152

  98. Yang Y, Yang CR, Han SJ, Daldello EM, Cho A, Martins JPS, Xia G, Conti M (2017) Maternal mRNAs with distinct 3' UTRs define the temporal pattern of Ccnb1 synthesis during mouse oocyte meiotic maturation. Genes Dev 31:1302–1307

  99. Yao R, Maeda T, Takada S, Noda T (2001) Identification of a PDZ domain containing Golgi protein, GOPC, as an interaction partner of frizzled. Biochem Biophys Res Commun 286:771–778

  100. Yao R, Ito C, Natsume Y, Sugitani Y, Yamanaka H, Kuretake S, Yanagida K, Sato A, Toshimori K, Noda T (2002) Lack of acrosome formation in mice lacking a Golgi protein, GOPC. Proc Natl Acad Sci U S A 99:11211–11216

  101. Yao K, Bian C, Zhao X (2017) Association of polycystic ovary syndrome with metabolic syndrome and gestational diabetes: aggravated complication of pregnancy. Experimental and therapeutic medicine 14:1271–1276

  102. Zdzalik D, Domanska A, Prorok P, Kosicki K, van den Born E, Falnes PO, Rizzo CJ, Guengerich FP, Tudek B (2015) Differential repair of etheno-DNA adducts by bacterial and human AlkB proteins. DNA repair 30:1–10

  103. Zhao ZB, Wu L, Xiong R, Wang LL, Zhang B, Wang C, Li H, Liang L, Chen SD (2014) MicroRNA-922 promotes tau phosphorylation by downregulating ubiquitin carboxy-terminal hydrolase L1 (UCHL1) expression in the pathogenesis of Alzheimer’s disease. Neuroscience 275:232–237

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Acknowledgments

We acknowledge the Central Instrumentation Facility, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India for providing necessary facilities during this study. We are thankful to the Department of Gynecology and Obstetrics, HAH Centenary Hospital, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India for the clinical collaboration in the study undertaken. We also acknowledge the Indian Council of Medical Research (ICMR) for the generous grant (Grant No: 5/4/7-8/2012/NCD-II) under which procurement of equipments used in this study was carried out.

Funding

University Grants Commission (UGC) supported Nadia Rashid by providing fellowship under the CSIR-UGC NET JRF Scheme.

Author information

The authors were responsible for the following: N.R: collected all the samples and related clinical information, did all experiments, tabulated and analyzed the data, did statistical and bioinformatic analysis, wrote the manuscript; A.N was the clinical collaborator of the study and reviewed the manuscript; S.K.J contributed to data interpretation and reviewed the manuscript; S.H.N provided help in real-time PCR experiments and data analysis; S.W. designed and conceptualized the study, provided research/instrumentation facilities, principal investigator of the study, analyzed the data, contributed to data interpretation and reviewed and finalized the manuscript.

Correspondence to Saima Wajid.

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The authors declare that they have no conflict of interest.

Informed consent

All subjects enrolled in this study signed the written informed consent prior to sample collection.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The present study was undertaken in clinical collaboration with the Hamdard Institute of Medical Sciences and Research (HIMSR) and ethical approval was obtained from the Institutional Ethics Committee of Jamia Hamdard (JHIEC), New Delhi, India (Ethical Approval July 01, 2015).

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Rashid, N., Nigam, A., Jain, S. et al. Proteomic sift through serum and endometrium profiles unraveled signature proteins associated with subdued fertility and dampened endometrial receptivity in women with polycystic ovary syndrome. Cell Tissue Res (2020). https://doi.org/10.1007/s00441-020-03171-3

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Keywords

  • PCOS
  • Infertility
  • Endometrium
  • Receptivity
  • Proteomics