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Anti-GAPDHS antibodies: a biomarker of immune infertility

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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.

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References

  • Bandivdekar AH (2014) Development of antifertility vaccine using sperm specific proteins. Indian J Med Res 140(Suppl):S73–S77

    PubMed  PubMed Central  Google Scholar 

  • 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 10:941–953

    Article  CAS  PubMed  Google Scholar 

  • Bozhedomov VA, Lipatova NA, Rokhlikov IM, Alexeev RA, Ushakova IV, Sukhikh GT (2014) Male fertility and varicocoele: role of immune factors. Andrology 2:51–58

    Article  CAS  PubMed  Google Scholar 

  • 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 8:813–818

    CAS  Google Scholar 

  • Bunch DO, Welch JE, Magyar PL, Eddy EM, O’Brien DA (1998) Glyceraldehyde 3-phosphate dehydrogenase-S protein distribution during mouse spermatogenesis. Biol Reprod 58:834–841

    Article  CAS  PubMed  Google Scholar 

  • Clark S, Naz RK (2013) Presence and incidence of izumo antibodies in sera of immunoinfertile women and men. Am J Reprod Immunol 69:256–263

    Article  CAS  PubMed  Google Scholar 

  • 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 444:29–36

    Article  CAS  PubMed  Google Scholar 

  • 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 26:132–134

    Article  CAS  PubMed  Google Scholar 

  • 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 11:42

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 1804:2207–2212

    Article  CAS  PubMed  Google Scholar 

  • 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 284:22703–22712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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–e1228

    Article  Google Scholar 

  • Gerais AS, Rushwan H (1992) Infertility in Africa. Pop Sci 12:25–46

    CAS  Google Scholar 

  • Katib AA, Al-Hawsawi K, Motair W, Bawa AM (2014) Secondary infertility and the aging male, overview. Cent Eur J Urol 67:184–188

    Google Scholar 

  • 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 24:197–204

    Article  CAS  PubMed  Google Scholar 

  • Kovac JR, Pastuszak AW, Lamb DJ (2013) The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility. Fertil Steril 99:998–1007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 8:84–88

    CAS  PubMed  Google Scholar 

  • 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 13:5403–5414

    Article  CAS  PubMed  Google Scholar 

  • Li HY, Zhang H (2013) Proteome analysis for profiling infertility markers in male mouse sperm after carbon ion radiation. Toxicology 306:85–92

    Article  CAS  PubMed  Google Scholar 

  • 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 97:445–452

    Article  CAS  PubMed  Google Scholar 

  • Mahdi BM, Salih WH, Caitano AE, Kadhum BM, Ibrahim DS (2011) Frequency of antisperm antibodies in infertile women. J Reprod Fertil 12:261–265

    CAS  Google Scholar 

  • 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 101:16501–16506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naz RK (1987) The fertilization antigen (FA-1) causes a reduction of fertility in actively immunized female rabbits. J Reprod Immunol 11:117–133

    Article  CAS  PubMed  Google Scholar 

  • Naz RK (2006) Effect of fertilization antigen (FA-1) DNA vaccine on fertility of female mice. Mol Reprod Dev 73:1473–1479

    Article  CAS  PubMed  Google Scholar 

  • Naz RK (2011) Antisperm contraceptive vaccines: where we are and where we are going? Am J Reprod Immunol 66:5–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naz RK (2014) Vaccine for human contraception targeting sperm Izumo protein and YLP12 dodecamer peptide. Protein Sci 23:857–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sen A, Kushnir VA, Barad DH, Gleicher N (2014) Endocrine autoimmune diseases and female infertility. Nat Rev Endocrinol 10:37–50

    Article  CAS  PubMed  Google Scholar 

  • Shibahara H, Koriyama J (2013) Methods for direct and indirect antisperm antibody testing. Methods Mol Biol 927:51–60

    Article  CAS  PubMed  Google Scholar 

  • 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 72:206–218

    Article  CAS  PubMed  Google Scholar 

  • 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 91:1245–1255

    Article  CAS  PubMed  Google Scholar 

  • 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 51:106–111

    Article  PubMed  Google Scholar 

  • 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 92:2020–2027

    Article  CAS  PubMed  Google Scholar 

  • 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 11:367–378

    Article  CAS  PubMed  Google Scholar 

  • 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 46:869–878

    Article  CAS  PubMed  Google Scholar 

  • 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 21:328–338

    CAS  PubMed  Google Scholar 

  • 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 73:1052–1060

    Article  CAS  PubMed  Google Scholar 

  • 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 59:518–524

    Article  CAS  PubMed  Google Scholar 

  • World Health Organization (2010) WHO laboratory manual for the examination and processing of human semen,5th edn. WHO, Geneva

    Google Scholar 

Download references

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.

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Authors and Affiliations

  1. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine Peking Union Medical College, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, No.5 Dong Dan San Tiao, Dongcheng, Beijing, People’s Republic of China

    Jun Fu, Rongyan Yao, Yanyun Luo, Wei Song, Shiying Miao & Linfang Wang

  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 Technique, Shandong Provincial Family Planning Institute of Science and Technology, Jinan, People’s Republic of China

    Dantong Yang & Yi Qiu

  3. National Health and Family Planning Key Laboratory of Male Reproductive Health, National Research Institute for Family Planning, World Health Organization Collaboration Centre for Research in Human Reproduction, Beijing, People’s Republic of China

    Yang Cao & Yiqun Gu

Authors
  1. Jun Fu
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  2. Rongyan Yao
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  3. Yanyun Luo
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  4. Dantong Yang
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  5. Yang Cao
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  6. Yi Qiu
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  7. Wei Song
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  8. Shiying Miao
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  9. Yiqun Gu
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  10. Linfang Wang
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Corresponding author

Correspondence to Linfang Wang.

Additional information

This work was supported by the grants from the National Important Research Plan of China (2012BAI31B08, 2012CB944902, and 2011CB944302) and the State Key Laboratory Special fund (2060204) of the Ministry of Science and Technology of China.

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Fu, J., Yao, R., Luo, Y. et al. Anti-GAPDHS antibodies: a biomarker of immune infertility. Cell Tissue Res 364, 199–207 (2016). https://doi.org/10.1007/s00441-016-2361-6

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  • DOI: https://doi.org/10.1007/s00441-016-2361-6

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