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N-glycoproteomic analysis of human follicular fluid during natural and stimulated cycles in patients undergoing in vitro fertilization

  • Lim, Hee-Joung (Forensic Science R&D Lab, Police Science Institute) ;
  • Seok, Ae Eun (Laboratory of Signal Transduction and Disease Biomarker Discovery, Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University) ;
  • Han, Jiyou (Department of Biological Sciences, Laboratory of Stem Cell Research and Biotechnology, Hyupsung University) ;
  • Lee, Jiyeong (Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University) ;
  • Lee, Sungeun (Research Institute of DONGDEOK Pharmaceutical) ;
  • Kang, Hee-Gyoo (Laboratory of Signal Transduction and Disease Biomarker Discovery, Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University) ;
  • Cha, Byung Heun (Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University) ;
  • Yang, Yunseok (Department of Obstetrics and Gynecology, Eulji University Hospital)
  • Received : 2017.04.21
  • Accepted : 2017.05.25
  • Published : 2017.06.30

Abstract

Objective: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. Methods: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. Results: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. Conclusion: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.

Keywords

References

  1. Nelson SM, Lawlor DA. Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles. PLoS Med 2011; 8:e1000386. https://doi.org/10.1371/journal.pmed.1000386
  2. Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertil Steril 2015;103:303-16. https://doi.org/10.1016/j.fertnstert.2014.11.015
  3. Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril 1978;30:255-68. https://doi.org/10.1016/S0015-0282(16)43508-9
  4. MacDougall MJ, Tan SL, Balen A, Jacobs HS. A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization. Hum Reprod 1993;8:233-7. https://doi.org/10.1093/oxfordjournals.humrep.a138029
  5. Angelucci S, Ciavardelli D, Di Giuseppe F, Eleuterio E, Sulpizio M, Tiboni GM, et al. Proteome analysis of human follicular fluid. Biochim Biophys Acta 2006;1764:1775-85. https://doi.org/10.1016/j.bbapap.2006.09.001
  6. Atiomo W, Khalid S, Parameshweran S, Houda M, Layfield R. Proteomic biomarkers for the diagnosis and risk stratification of polycystic ovary syndrome: a systematic review. BJOG 2009;116: 137-43. https://doi.org/10.1111/j.1471-0528.2008.02041.x
  7. Ducolomb Y, Gonzalez-Marquez H, Fierro R, Jimenez I, Casas E, Flores D, et al. Effect of porcine follicular fluid proteins and peptides on oocyte maturation and their subsequent effect on in vitro fertilization. Theriogenology 2013;79:896-904. https://doi.org/10.1016/j.theriogenology.2013.01.024
  8. Estes SJ, Ye B, Qiu W, Cramer D, Hornstein MD, Missmer SA. A proteomic analysis of IVF follicular fluid in women https://doi.org/10.1016/j.fertnstert.2008.08.120
  9. Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. Proteomic analysis of peritoneal fluid in fertile and infertile women with endometriosis. J Reprod Med 2009;54:32-40.
  10. Jarkovska K, Martinkova J, Liskova L, Halada P, Moos J, Rezabek K, et al. Proteome mining of human follicular fluid reveals a crucial role of complement cascade and key biological pathways in women undergoing in vitro fertilization. J Proteome Res 2010;9: 1289-301. https://doi.org/10.1021/pr900802u
  11. Georgiou AS, Sostaric E, Wong CH, Snijders AP, Wright PC, Moore HD, et al. Gametes alter the oviductal secretory proteome. Mol Cell Proteomics 2005;4:1785-96. https://doi.org/10.1074/mcp.M500119-MCP200
  12. Curry TE Jr, Dean DD, Sanders SL, Pedigo NG, Jones PB. The role of ovarian proteases and their inhibitors in ovulation. Steroids 1989;54:501-21. https://doi.org/10.1016/0039-128X(89)90044-5
  13. Yokota K, Hirano T, Urata N, Yamauchi N, Hattori MA. Upregulation of P-glycoprotein activity in porcine oocytes and granulosa cells during in vitro maturation. J Reprod Dev 2011;57:322-6. https://doi.org/10.1262/jrd.10-137M
  14. Clark GF. Functional glycosylation in the human and mammalian uterus. Fertil Res Pract 2015;1:17. https://doi.org/10.1186/s40738-015-0007-0
  15. Daikoku T, Tranguch S, Friedman DB, Das SK, Smith DF, Dey SK. Proteomic analysis identifies immunophilin FK506 binding protein 4 (FKBP52) as a downstream target of Hoxa10 in the periimplantation mouse uterus. Mol Endocrinol 2005;19:683-97. https://doi.org/10.1210/me.2004-0332
  16. Aitken RJ, Nixon B, Lin M, Koppers AJ, Lee YH, Baker MA. Proteomic changes in mammalian spermatozoa during epididymal maturation. Asian J Androl 2007;9:554-64. https://doi.org/10.1111/j.1745-7262.2007.00280.x
  17. Peddinti D, Nanduri B, Kaya A, Feugang JM, Burgess SC, Memili E. Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility. BMC Syst Biol 2008;2:19. https://doi.org/10.1186/1752-0509-2-19
  18. Yoon SJ, Rahman MS, Kwon WS, Ryu DY, Park YJ, Pang MG. Proteomic identification of cryostress in epididymal spermatozoa. J Anim Sci Biotechnol 2016;7:67. https://doi.org/10.1186/s40104-016-0128-2
  19. Bedaiwy M, Shahin AY, AbulHassan AM, Goldberg JM, Sharma RK, Agarwal A, et al. Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles. Reprod Biomed Online 2007;15:321-5. https://doi.org/10.1016/S1472-6483(10)60346-X
  20. Spitzer D, Murach KF, Lottspeich F, Staudach A, Illmensee K. Different protein patterns derived from follicular fluid of mature and immature human follicles. Hum Reprod 1996;11:798-807. https://doi.org/10.1093/oxfordjournals.humrep.a019257
  21. Anderson NL, Anderson NG. Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis 1998;19:1853-61. https://doi.org/10.1002/elps.1150191103
  22. Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 2002;1:845-67. https://doi.org/10.1074/mcp.R200007-MCP200
  23. Hanrieder J, Nyakas A, Naessen T, Bergquist J. Proteomic analysis of human follicular fluid using an alternative bottom-up approach. J Proteome Res 2008;7:443-9. https://doi.org/10.1021/pr070277z
  24. Lee HC, Lee SW, Lee KW, Lee SW, Cha KY, Kim KH, et al. Identification of new proteins in follicular fluid from mature human follicles by direct sample rehydration method of two-dimensional polyacrylamide gel electrophoresis. J Korean Med Sci 2005;20: 456-60. https://doi.org/10.3346/jkms.2005.20.3.456
  25. Hughes SC, Mason HD, Franks S, Holly JM. The insulin-like growth factors (IGFs) in follicular fluid are predominantly bound in the ternary complex. J Endocrinol 1997;155:R1-4. https://doi.org/10.1677/joe.0.155R001
  26. Wujek P, Kida E, Walus M, Wisniewski KE, Golabek AA. N-glycosylation is crucial for folding, trafficking, and stability of human tripeptidyl- peptidase I. J Biol Chem 2004;279:12827-39. https://doi.org/10.1074/jbc.M313173200
  27. Schweigert FJ, Gericke B, Wolfram W, Kaisers U, Dudenhausen JW. Peptide and protein profiles in serum and follicular fluid of women undergoing IVF. Hum Reprod 2006;21:2960-8. https://doi.org/10.1093/humrep/del257
  28. Ceciliani F, Giordano A, Spagnolo V. The systemic reaction during inflammation: the acute-phase proteins. Protein Pept Lett 2002; 9:211-23. https://doi.org/10.2174/0929866023408779
  29. de Boer JP, Creasey AA, Chang A, Abbink JJ, Roem D, Eerenberg AJ, et al. Alpha-2-macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: studies using a baboon model. Infect Immun 1993;61:5035-43.
  30. Tse JY, Chiu PC, Lee KF, Seppala M, Koistinen H, Koistinen R, et al. The synthesis and fate of glycodelin in human ovary during folliculogenesis. Mol Hum Reprod 2002;8:142-8. https://doi.org/10.1093/molehr/8.2.142
  31. Das T, Chattopadhyay R, Ghosh S, Goswami S, Chattopadhyay D, Chakravarty B, et al. Role of an estrogen-upregulated 64.0-kDa uterine fluid glycoprotein in improving fertility in women. Fertil Steril 2007;87:343-50. https://doi.org/10.1016/j.fertnstert.2006.07.1500
  32. Dai G, Lu G. Different protein expression patterns associated with polycystic ovary syndrome in human follicular fluid during controlled ovarian hyperstimulation. Reprod Fertil Dev 2012;24: 893-904. https://doi.org/10.1071/RD11201
  33. Kim YS, Kim MS, Lee SH, Choi BC, Lim JM, Cha KY, et al. Proteomic analysis of recurrent spontaneous abortion: identification of an inadequately expressed set of proteins in human follicular fluid. Proteomics 2006;6:3445-54. https://doi.org/10.1002/pmic.200500775
  34. Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, et al. Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol 2009;27:378-86. https://doi.org/10.1038/nbt.1532
  35. Echan LA, Tang HY, Ali-Khan N, Lee K, Speicher DW. Depletion of multiple high-abundance proteins improves protein profiling capacities of human serum and plasma. Proteomics 2005;5: 3292-303. https://doi.org/10.1002/pmic.200401228
  36. Larsen MR, Jensen SS, Jakobsen LA, Heegaard NH. Exploring the sialiome using titanium dioxide chromatography and mass spectrometry. Mol Cell Proteomics 2007;6:1778-87. https://doi.org/10.1074/mcp.M700086-MCP200
  37. Fortune JE. Ovarian follicular growth and development in mammals. Biol Reprod 1994;50:225-32. https://doi.org/10.1095/biolreprod50.2.225
  38. Nayudu PL, Lopata A, Jones GM, Gook DA, Bourne HM, Sheather SJ, et al. An analysis of human oocytes and follicles from stimulated cycles: oocyte morphology and associated follicular fluid characteristics. Hum Reprod 1989;4:558-67. https://doi.org/10.1093/oxfordjournals.humrep.a136944
  39. Kuo MW, Wang CH, Wu HC, Chang SJ, Chuang YJ. Soluble THSD7A is an N-glycoprotein that promotes endothelial cell migration and tube formation in angiogenesis. PLoS One 2011;6: e29000. https://doi.org/10.1371/journal.pone.0029000
  40. Tahboub R, Arafah BM. Sex steroids and the thyroid. Best Pract Res Clin Endocrinol Metab 2009;23:769-80. https://doi.org/10.1016/j.beem.2009.06.005
  41. Poppe K, Velkeniers B, Glinoer D. The role of thyroid autoimmunity in fertility and pregnancy. Nat Clin Pract Endocrinol Metab 2008;4:394-405. https://doi.org/10.1038/ncpendmet0846
  42. Stuckey BG, Yeap D, Turner SR. Thyroxine replacement during super-ovulation for in vitro fertilization: a potential gap in management? Fertil Steril 2010;93:2414.e1-3.
  43. Lee S, Kang DW, Hudgins-Spivey S, Krust A, Lee EY, Koo Y, et al. Theca-specific estrogen receptor-alpha knockout mice lose fertility prematurely. Endocrinology 2009;150:3855-62. https://doi.org/10.1210/en.2008-1774
  44. Cooke NE, David EV. Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. J Clin Invest 1985;76:2420-4. https://doi.org/10.1172/JCI112256
  45. Nielsen HK, Brixen K, Bouillon R, Mosekilde L. Changes in biochemical markers of osteoblastic activity during the menstrual cycle. J Clin Endocrinol Metab 1990;70:1431-7. https://doi.org/10.1210/jcem-70-5-1431
  46. Kushner I. The acute phase response: an overview. Methods Enzymol 1988;163:373-83.
  47. Schepeler T, Mansilla F, Christensen LL, Orntoft TF, Andersen CL. Clusterin expression can be modulated by changes in TCF1-mediated Wnt signaling. J Mol Signal 2007;2:6. https://doi.org/10.1186/1750-2187-2-6
  48. Orvieto R. Controlled ovarian hyperstimulation: an inflammatory state. J Soc Gynecol Investig 2004;11:424-6. https://doi.org/10.1016/j.jsgi.2004.05.001
  49. Orvieto R, Zagatsky I, Yulzari-Roll V, La Marca A, Fisch B. Substituting human chorionic gonadotropin by gonadotropin-releasing hormone agonist to trigger final follicular maturation, during controlled ovarian hyperstimulation, results in less systemic inflammation. Gynecol Endocrinol 2006;22:437-40. https://doi.org/10.1080/09513590600881339
  50. Revelli A, Delle Piane L, Casano S, Molinari E, Massobrio M, Rinaudo P. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol 2009;7:40. https://doi.org/10.1186/1477-7827-7-40
  51. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001;280:C1358-66. https://doi.org/10.1152/ajpcell.2001.280.6.C1358
  52. Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL. Insulinlike growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 2002;277:38205-11. https://doi.org/10.1074/jbc.M203781200
  53. Agrawal R, Sladkevicius P, Engmann L, Conway GS, Payne NN, Bekis J, et al. Serum vascular endothelial growth factor concentrations and ovarian stromal blood flow are increased in women with polycystic ovaries. Hum Reprod 1998;13:651-5. https://doi.org/10.1093/humrep/13.3.651
  54. Bora NS, Kaliappan S, Jha P, Xu Q, Sohn JH, Dhaulakhandi DB, et al. Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H. J Immunol 2006;177:1872-8. https://doi.org/10.4049/jimmunol.177.3.1872
  55. Girardi G, Yarilin D, Thurman JM, Holers VM, Salmon JE. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 2006;203:2165-75. https://doi.org/10.1084/jem.20061022
  56. Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, et al. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A 2006;103: 2328-33. https://doi.org/10.1073/pnas.0408835103
  57. Jarkovska K, Kupcova Skalnikova H, Halada P, Hrabakova R, Moos J, Rezabek K, et al. Development of ovarian hyperstimulation syndrome: interrogation of key proteins and biological processes in human follicular fluid of women undergoing in vitro fertilization. Mol Hum Reprod 2011;17:679-92. https://doi.org/10.1093/molehr/gar047
  58. Wu R, Van der Hoek KH, Ryan NK, Norman RJ, Robker RL. Macrophage contributions to ovarian function. Hum Reprod Update 2004;10:119-33. https://doi.org/10.1093/humupd/dmh011
  59. Kruger AJ, Yang C, Tam SW, Hinerfeld D, Evans JE, Green KM, et al. Haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and LEW1.WR1 rats. Exp Biol Med (Maywood) 2010;235:1328-37. https://doi.org/10.1258/ebm.2010.010150

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