Skip to main content
SpringerLink
Log in

The relevance of ANXA5 genetic variants on male fertility

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the effect of the anticoagulation factor annexin A5 on male fertility and to provide perspective on the influence of members of the coagulation cascade on fertility.

Methods

Patients with normozoospermia and with unexplained severe oligozoospermia were retrospectively selected and their genomic DNA sequenced for the promoter region of ANXA5. The genotypes proportions and the odds ratio for carriership of the haplotype M2 were compared between the groups and population control. The clinical data used were gathered from parameters determined during routine clinical assessment and were compared between carriers and non-carriers within the patient groups.

Results

The carrier rates for the haplotype M2/ANXA5 were of 25.73%, 20.81%, and 15.3% in the severe oligozoospermic, the normozoospermic, and the general population control groups, respectively. The OR between patients groups was of 1.31 (95% CI 0.88 to 1.96 p = 0.176). Oligozoospermic and normozoospermic patients compared with the control group had an OR of 1.9 (95% CI 1.33 to 2.73 p < 0.001) and 1.45 (95% CI 0.99 to 2.10 p = 0.054) respectively. The clinical parameters that differed between the carriers and non-carriers of the haplotype M2/ANXA5 were prolactin, α-glucosidase, and fructose. The differences were only statistically significant in the normozoospermic group.

Conclusions

Athough the infertile patient groups had a higher prevalence of promoter variants, we could not demonstrate any biologically relevant effect of lower levels of annexin A5 on most male fertility parameters. A deficiency in an anticoagulation factor does not seem to impact male fertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Simcox LE, Ormesher L, Tower C, Greer IA. Thrombophilia and pregnancy complications. Int J Mol Sci. 2015;16:28418–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cohn DM, Repping S, Büller HR, Meijers JCM, Middeldorp S. Increased sperm count may account for high population frequency of factor V Leiden. J Thromb Haemost [Internet]. 2010;8:513–6. https://doi.org/10.1111/j.1538-7836.2009.03710.x.

    Article  CAS  Google Scholar 

  3. Yapijakis C, Pachis N, Avgoustidis D, Adamopoulou M, Serefoglou Z. Mutations of two major coagulation factors are not associated with male infertility. In Vivo (Brooklyn) [Internet]. 2016;30:927–30. https://doi.org/10.21873/invivo.11015.

  4. Bogdanova N, Horst J, Chlystun M, Croucher PJP, Nebel A, Bohring A, et al. A common haplotype of the annexin A5 (ANXA5) gene promoter is associated with recurrent pregnancy loss. Hum Mol Genet [Internet]. 2007;16:573–8. https://doi.org/10.1093/hmg/ddm017.

    Article  CAS  Google Scholar 

  5. Markoff A, Gerdes S, Feldner S, Bogdanova N, Gerke V, Grandone E. Reduced allele specific annexin A5 mRNA levels in placentas carrying the M2/ANXA5 allele. Placenta [Internet]. 2010;31:937–40. Elsevier Ltd. https://doi.org/10.1016/j.placenta.2010.08.002.

    Article  CAS  Google Scholar 

  6. Chinni E, Tiscia GL, Colaizzo D, Vergura P, Margaglione M, Grandone E.. Annexin V expression in human placenta is influenced by the carriership of the common haplotype M2. Fertil Steril [Internet]. 2009;[cited 2015 Jul 3];91:940–2. https://doi.org/10.1016/j.fertnstert.2007.12.056.

  7. Tüttelmann F, Ivanov P, Dietzel C, Sofroniou A, Tsvyatkovska TM, Komsa-Penkova RS, et al. Further insights into the role of the annexin A5 M2 haplotype as recurrent pregnancy loss factor, assessing timing of miscarriage and partner risk. Fertil Steril [Internet]. 2013;100:1321–5. https://doi.org/10.1016/j.fertnstert.2013.06.046.

  8. Rogenhofer N, Engels L, Bogdanova N, Tüttelmann F, Markoff A, Thaler C. Paternal and maternal carriage of the annexin A5 M2 haplotype are equal risk factors for recurrent pregnancy loss: a pilot study. Fertil Steril [Internet]. 2012;98:383–8. https://doi.org/10.1016/j.fertnstert.2012.04.026.

  9. Demetriou C, Abu-amero S, White S, Peskett E, Markoff A, Stanier P, et al. Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion. Reprod Biomed Online [Internet]. 2015;31:681–8. https://doi.org/10.1016/j.rbmo.2015.07.004.

  10. Li J, Liu F, Liu X, Liu J, Zhu P, Wan F, et al. Mapping of the human testicular proteome and its relationship with that of the epididymis and spermatozoa. Mol Cell Proteomics [Internet]. 2011;10:M110.004630–0. https://doi.org/10.1074/mcp.M110.004630.

  11. Guyonnet B, Dacheux F, Dacheux J-L, Gatti J-L. The Epididymal transcriptome and proteome provide some insights into new epididymal regulations. J Androl [Internet]. 2011;32:651–64. https://doi.org/10.2164/jandrol.111.013086.

    Article  CAS  Google Scholar 

  12. Haigler HT, Christmas P. Annexin 1 is secreted by the human prostate. Biochem Soc Trans [Internet]. 1990 [cited 2016 Aug 25];18:1104–6. Available from: https://doi.org/10.1042/bst0181104.

  13. Amaral A, Castillo J, Ramalho-Santos J, Oliva R. The combined human sperm proteome: cellular pathways and implications for basic and clinical science. Hum Reprod Update [Internet]. 2014;20:40–62. https://doi.org/10.1093/humupd/dmt046.

    Article  CAS  Google Scholar 

  14. Giambanco I, Pula G, Ceccarelli P, Bianchi R, Donato R. Immunohistochemical localization of annexin V (CaBP33) in rat organs. J Histochem Cytochem [Internet]. 1991;39:1189–98. https://doi.org/10.1177/39.9.1833446.

    Article  CAS  Google Scholar 

  15. Kawaminami M, Kawamoto T, Tanabe T, Yamaguchi K, Mutoh K, Kurusu S, et al. Immunocytochemical localization of annexin 5, a calcium-dependent phospholipid-binding protein, in rat endocrine organs. Cell Tissue Res [Internet]. 1998 [cited 2015 Jul 3];292:85;292:85. https://doi.org/10.1007/s004410051037.

    Article  CAS  Google Scholar 

  16. Arruda J, Viana Neto A, Souza C, Martins J, Moreno FB, Moreira ACO, et al. Major proteins of the seminal plasma of New Zealand White rabbits and association with semen criteria. 10th World Rabbit Congr World Rabbit Sci Assoc [Internet]. 2012;82:395–9 Available from: https://world-rabbit-science.com/WRSA-Proceedings/Congress-2012-Egypt/Papers/02-Reproduction/R-Arruda-Alencar.pdf.

    Google Scholar 

  17. WHO. WHO laboratory manual for the examination and processing of human semen. Edition, V. 2010. Available from: http://whqlibdoc.who.int/publications/2010/9789241547789_eng.pdf

  18. Krawczak M, Nikolaus S, von Eberstein H, Croucher PJP, El Mokhtari NE, PopGen SS. Population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships. Community Genet. 2006;9:55–61. https://doi.org/10.1159/000090694.

  19. Rogenhofer N, Markoff A, Wagner A, Klein H-G, Petroff D, Schleussner E, et al. Lessons from the EThIGII trial. Clin Appl Thromb [Internet]. 2017;23:27–33. https://doi.org/10.1177/1076029616658117.

    Article  CAS  Google Scholar 

  20. Rousset F. genepop’007: a complete re-implementation of the genepop software for Windows and Linux. Mol Ecol Resour [Internet]. 2008;8:103–6. https://doi.org/10.1111/j.1471-8286.2007.01931.x.

    Article  Google Scholar 

  21. Cooper TG. Secretory proteins from the epididymis and their clinical relevance. Andrologia [Internet]. 1990;22(Suppl 1):155–65 Available from: 2132067.

    Google Scholar 

  22. Kawaminami M, Tanaka K, Asawa T, Osugi S, Kawauchi ’ H, Kurusu S, et al. Association of annexin V with prolactin in the rat anterior pituitary gland. Biochem Biophys Res Commun. 1992;186:894–9.

    Article  CAS  PubMed  Google Scholar 

  23. Kawaminami M, Okazaki K, Uchida S, Marumoto N, Takehara K, Kurusu S, et al. Intrapituitary distribution and effects of annexin 5 on prolactin release. Endocrine. 1996;5:9–14.

    Article  CAS  PubMed  Google Scholar 

  24. Kawaminami M, Shibata Y, Yaji A, Kurusu S, Hashimoto I. Prolactin inhibits annexin 5 expression and apoptosis in the Corpus luteum of pseudopregnant rats: involvement of local gonadotropin-releasing hormone. Endocrinology [Internet]. 2003;144:3625–31. https://doi.org/10.1210/en.2003-0118.

    Article  CAS  Google Scholar 

  25. Kawaminami M, Senda A, Etoh S, Miyaoka H, Kurusu S, Hashimoto I. Annexin 5 inhibits thyrotropin releasing hormone (TRH) stimulated prolactin release in the primary culture of rat anterior pituitary cells. Endocr J. 2004;51:349–54.

    Article  CAS  PubMed  Google Scholar 

  26. Rastrelli G, Corona G, Maggi M. The role of prolactin in andrology: what is new? Rev Endocr Metab Disord [Internet]. 2015;16:233–48. https://doi.org/10.1007/s11154-015-9322-3.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Michelina Kierzek for language editing the manuscript and Albrecht Röpke for the laboratory work.

Funding

Full doctorate fellowship for Heloisa Lopes Lavorato was provided by the Brazilian program Science without Borders by the Brazilian funding agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under the process 206742/2014-2. A STIBET-DAAD fellowship was awarded to HL by the University Münster. Experimental work was supported by the DFG Clinical Research Unit 326.

Author information

Authors and Affiliations

  1. Centre of Reproductive Medicine and Andrology, University of Münster, Münster, Germany

    Heloisa Lopes Lavorato, Sabine Kliesch & Stefan Schlatt

  2. Institute of Human Genetics, University of Münster, Münster, Germany

    Arseni Markoff, Valeria Altholz, Nadja Bogdanova & Peter Wieacker

Authors
  1. Heloisa Lopes Lavorato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arseni Markoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valeria Altholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nadja Bogdanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Wieacker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sabine Kliesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stefan Schlatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan Schlatt.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lavorato, H.L., Markoff, A., Altholz, V. et al. The relevance of ANXA5 genetic variants on male fertility. J Assist Reprod Genet 36, 1355–1359 (2019). https://doi.org/10.1007/s10815-019-01458-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-019-01458-1

Keywords

Search

Navigation