Advertisement

Cell and Tissue Research

, Volume 364, Issue 1, pp 199–207 | Cite as

Anti-GAPDHS antibodies: a biomarker of immune infertility

  • Jun Fu
  • Rongyan Yao
  • Yanyun Luo
  • Dantong Yang
  • Yang Cao
  • Yi Qiu
  • Wei Song
  • Shiying Miao
  • Yiqun Gu
  • Linfang WangEmail author
Regular Article

Abstract

Numerous investigations have focused on the detection of antisperm antibodies, which have a naturally occurring impact on male and female fertility. In this study, spermatogenic glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) was considered to be a candidate biomarker of immune infertility. The concentrations of anti–GAPDHS antibodies in the sera of sterile individuals and fertile couples were measured by enzyme-linked immunosorbent assay. Sera were collected from immune infertile (n = 175) and fertile (n = 237) individuals and were screened by tray agglutination tests (TAT). Infertile sera were further divided into two groups according to the serum titers obtained by TAT (titers ≤ 1:8, n = 58; titers > 1:8, n = 117). The concentrations of anti–GAPDHS antibodies were significantly higher in the immune infertile group than in the fertile group and were much higher with regard to the increased degrees of sperm agglutination (titers > 1:8). Surprisingly, we found statistically significantly higher concentrations of antibodies in the sera of infertile men than in those of infertile women, and a similar statistical result was obtained in the sera when primary infertility was compared with secondary infertility. Thus, anti–GAPDHS antibodies seem to be a sensitive parameter in immune infertile detection and might be one of the main factors causing immune infertility. This factor might be valuable as an indicator in the clinical diagnosis and monitoring treatment of infertility.

Keywords

Immune infertility GAPDHS ELISA Antisperm antibodies Primary infertility 

Notes

Acknowledgments

The authors thank Hefeng Huang for the collection of sera, and Wei Han for help with the statistical analysis of the data. The Core Instrument Facility of the Institute of Basic Medical Sciences provided instrumental assistance for the research.

References

  1. Bandivdekar AH (2014) Development of antifertility vaccine using sperm specific proteins. Indian J Med Res 140(Suppl):S73–S77PubMedPubMedCentralGoogle Scholar
  2. Batruch I, Lecker I, Kagedan D, Smith CR, Mullen BJ, Grober E, Lo KC, Diamandis EP, Jarvi KA (2011) Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system. J Proteome Res 10:941–953CrossRefPubMedGoogle Scholar
  3. Bozhedomov VA, Lipatova NA, Rokhlikov IM, Alexeev RA, Ushakova IV, Sukhikh GT (2014) Male fertility and varicocoele: role of immune factors. Andrology 2:51–58CrossRefPubMedGoogle Scholar
  4. Brazdova A, Vermachova M, Zidkova J, Ulcova-Gallova Z, Peltre G (2013) Immunodominant semen proteins I: new patterns of sperm proteins related to female immune infertility. Cent Eur J Biol 8:813–818Google Scholar
  5. Bunch DO, Welch JE, Magyar PL, Eddy EM, O’Brien DA (1998) Glyceraldehyde 3-phosphate dehydrogenase-S protein distribution during mouse spermatogenesis. Biol Reprod 58:834–841CrossRefPubMedGoogle Scholar
  6. Clark S, Naz RK (2013) Presence and incidence of izumo antibodies in sera of immunoinfertile women and men. Am J Reprod Immunol 69:256–263CrossRefPubMedGoogle Scholar
  7. Cui D, Han G, Shang Y, Liu C, Xia L, Li L, Yi S (2015) Antisperm antibodies in infertile men and their effect on semen parameters: a systematic review and meta-analysis. Clin Chim Acta 444:29–36CrossRefPubMedGoogle Scholar
  8. Davari Tanha F, Mohseni M, Ghajarzadeh M (2014) Sexual function in women with primary and secondary infertility in comparison with controls. Int J Impot Res 26:132–134CrossRefPubMedGoogle Scholar
  9. Dorosh A, Tepla O, Zatecka E, Ded L, Koci K, Peknicova J (2013) Expression analysis of MND1/GAJ, SPATA22, GAPDHS and ACR genes in testicular biopsies from non-obstructive azoospermia (NOA) patients. Reprod Biol Endocrinol 11:42CrossRefPubMedPubMedCentralGoogle Scholar
  10. Elkina YL, Kuravsky ML, El’darov MA, Stogov SV, Muronetz VI, Schmalhausen EV (2010) Recombinant human sperm-specific glyceraldehyde-3-phosphate dehydrogenase: structural basis for enhanced stability. Biochim Biophys Acta 1804:2207–2212CrossRefPubMedGoogle Scholar
  11. Frayne J, Taylor A, Cameron G, Hadfield AT (2009) Structure of insoluble rat sperm glyceraldehyde-3-phosphate dehydrogenase (GAPDH) via heterotetramer formation with Escherichia coli GAPDH reveals target for contraceptive design. J Biol Chem 284:22703–22712CrossRefPubMedPubMedCentralGoogle Scholar
  12. Fu J, Wang Y, Fok KL, Yang D, Qiu Y, Chan HC, Koide SS, Miao S, Wang L (2012) Anti-ACTL7a antibodies: a cause of infertility. Fertil Steril 97:e1221–e1228CrossRefGoogle Scholar
  13. Gerais AS, Rushwan H (1992) Infertility in Africa. Pop Sci 12:25–46Google Scholar
  14. Katib AA, Al-Hawsawi K, Motair W, Bawa AM (2014) Secondary infertility and the aging male, overview. Cent Eur J Urol 67:184–188Google Scholar
  15. Kortebani G, Gonzales GF, Barrera C, Mazzolli AB (1992) Leucocyte populations in semen and male accessory gland function: relationship with antisperm antibodies and seminal quality. Andrologia 24:197–204CrossRefPubMedGoogle Scholar
  16. Kovac JR, Pastuszak AW, Lamb DJ (2013) The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility. Fertil Steril 99:998–1007CrossRefPubMedPubMedCentralGoogle Scholar
  17. Lahteenmaki A (1993) In-vitro fertilization in the presence of antisperm antibodies detected by the mixed antiglobulin reaction (MAR) and the tray agglutination test (TAT). Hum Reprod 8:84–88PubMedGoogle Scholar
  18. Legare C, Droit A, Fournier F, Bourassa S, Force A, Cloutier F, Tremblay R, Sullivan R (2014) Investigation of male infertility using quantitative comparative proteomics. J Proteome Res 13:5403–5414CrossRefPubMedGoogle Scholar
  19. Li HY, Zhang H (2013) Proteome analysis for profiling infertility markers in male mouse sperm after carbon ion radiation. Toxicology 306:85–92CrossRefPubMedGoogle Scholar
  20. Li H, Ding X, Guo C, Guan H, Xiong C (2012) Immunization of male mice with B-cell epitopes in transmembrane domains of CatSper1 inhibits fertility. Fertil Steril 97:445–452CrossRefPubMedGoogle Scholar
  21. Mahdi BM, Salih WH, Caitano AE, Kadhum BM, Ibrahim DS (2011) Frequency of antisperm antibodies in infertile women. J Reprod Fertil 12:261–265Google Scholar
  22. Miki K, Qu W, Goulding EH, Willis WD, Bunch DO, Strader LF, Perreault SD, Eddy EM, O’Brien DA (2004) Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility. Proc Natl Acad Sci U S A 101:16501–16506CrossRefPubMedPubMedCentralGoogle Scholar
  23. Naz RK (1987) The fertilization antigen (FA-1) causes a reduction of fertility in actively immunized female rabbits. J Reprod Immunol 11:117–133CrossRefPubMedGoogle Scholar
  24. Naz RK (2006) Effect of fertilization antigen (FA-1) DNA vaccine on fertility of female mice. Mol Reprod Dev 73:1473–1479CrossRefPubMedGoogle Scholar
  25. Naz RK (2011) Antisperm contraceptive vaccines: where we are and where we are going? Am J Reprod Immunol 66:5–12CrossRefPubMedPubMedCentralGoogle Scholar
  26. Naz RK (2014) Vaccine for human contraception targeting sperm Izumo protein and YLP12 dodecamer peptide. Protein Sci 23:857–868CrossRefPubMedPubMedCentralGoogle Scholar
  27. Sen A, Kushnir VA, Barad DH, Gleicher N (2014) Endocrine autoimmune diseases and female infertility. Nat Rev Endocrinol 10:37–50CrossRefPubMedGoogle Scholar
  28. Shibahara H, Koriyama J (2013) Methods for direct and indirect antisperm antibody testing. Methods Mol Biol 927:51–60CrossRefPubMedGoogle Scholar
  29. Vazquez-Levin MH, Marin-Briggiler CI, Veaute C (2014) Antisperm antibodies: invaluable tools toward the identification of sperm proteins involved in fertilization. Am J Reprod Immunol 72:206–218CrossRefPubMedGoogle Scholar
  30. Veaute C, Furlong LI, Bronson R, Harris JD, Vazquez-Levin MH (2009) Acrosin antibodies and infertility. I. Detection of antibodies towards proacrosin/acrosin in women consulting for infertility and evaluation of their effects upon the sperm protease activities. Fertil Steril 91:1245–1255CrossRefPubMedGoogle Scholar
  31. Vernekar VJ, Bandivdekar AH, Raghavan VP, Kamada M, Koide SS (2004) Studies with synthetic peptides of 80 kDa human sperm antigen (80 kDa HSA). Am J Reprod Immunol 51:106–111CrossRefPubMedGoogle Scholar
  32. Wang Y, Zhang N, Zhang XD, Miao SY, Zong SD, Koide SS, Wang LF (2009) Experimental immunological infertility effect of anti-GAPDH-2 antibodies on the fertility of female mice. Fertil Steril 92:2020–2027CrossRefPubMedGoogle Scholar
  33. Warwas M, Wendt V, Shams-Borhan G, Dietl T (1979) Anti-acrosin antibodies in sera, colostrum and genital organs of vaccinated ewes: estimation and correlation with fertility. Andrologia 11:367–378CrossRefPubMedGoogle Scholar
  34. Welch JE, Schatte EC, O’Brien DA, Eddy EM (1992) Expression of a glyceraldehyde 3-phosphate dehydrogenase gene specific to mouse spermatogenic cells. Biol Reprod 46:869–878CrossRefPubMedGoogle Scholar
  35. Welch JE, Brown PL, O’Brien DA, Magyar PL, Bunch DO, Mori C, Eddy EM (2000) Human glyceraldehyde 3-phosphate dehydrogenase-2 gene is expressed specifically in spermatogenic cells. J Androl 21:328–338PubMedGoogle Scholar
  36. Welch JE, Barbee RR, Magyar PL, Bunch DO, O’Brien DA (2006) Expression of the spermatogenic cell-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) in rat testis. Mol Reprod Dev 73:1052–1060CrossRefPubMedGoogle Scholar
  37. Williams J, Samuel A, Naz RK (2008) Presence of antisperm antibodies reactive with peptide epitopes of FA-1 and YLP12 in sera of immunoinfertile women. Am J Reprod Immunol 59:518–524CrossRefPubMedGoogle Scholar
  38. World Health Organization (2010) WHO laboratory manual for the examination and processing of human semen,5th edn. WHO, GenevaGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jun Fu
    • 1
  • Rongyan Yao
    • 1
  • Yanyun Luo
    • 1
  • Dantong Yang
    • 2
  • Yang Cao
    • 3
  • Yi Qiu
    • 2
  • Wei Song
    • 1
  • Shiying Miao
    • 1
  • Yiqun Gu
    • 3
  • Linfang Wang
    • 1
    Email author
  1. 1.State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesBeijingPeople’s Republic of China
  2. 2.Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Shandong Provincial Key Laboratory for Improving Birth Outcome TechniqueShandong Provincial Family Planning Institute of Science and TechnologyJinanPeople’s Republic of China
  3. 3.National Health and Family Planning Key Laboratory of Male Reproductive Health, National Research Institute for Family PlanningWorld Health Organization Collaboration Centre for Research in Human ReproductionBeijingPeople’s Republic of China

Personalised recommendations