Skip to main content

Advertisement

SpringerLink
Log in

Seminal Plasma and Serum Afamin Levels Are Associated with Infertility in Men with Oligoasthenoteratozoospermia

  • Male Reproduction: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

A Correction to this article was published on 22 February 2021

This article has been updated

Abstract

The plasma glycoprotein afamin has been previously identified as an alternative carrier protein for vitamin E in extravascular fluids such as plasma and cerebrospinal, ovarian follicular, and seminal fluids. However, to date, no study has established a relationship between afamin levels and infertility in women or men. The purposes of our study were (i) to assess the level of afamin in serum and seminal fluids in infertile men compared to healthy controls and (ii) to study the association between polymorphisms in afamin genes and male infertility. This observational, prospective study evaluated the afamin levels in serum and seminal fluids from infertile men (n = 39) and compared them to those in healthy controls (n = 30). We studied the association between single-nucleotide polymorphisms (SNPs) in the 5`-untranslated region (5`-UTR) of the afamin gene and infertility and analyzed a total of 1000 base pairs from the untranslated region of the afamin gene. Subjects with low sperm motility and low sperm concentration had higher median seminal afamin (18.9 ± 2.9 ng/mg of proteins) and serum afamin concentrations (24.1 ± 4.0 ng/mg of proteins) than subjects with normal sperm parameters (10.6 ± 1.4 ng/mg of proteins) (p < 0.02) (15.6 ± 1.4 ng/mg of proteins) (p < 0.002). A total of five different polymorphisms were found, including one deletion and four single-nucleotide polymorphisms (SNPs). A new transversion (A/T) (position 4:73481093) was identified in an oligoasthenoteratozoospermic patient and was associated with high levels of afamin in plasma and seminal fluids. The prevalence of this variant in our study in the case homozygous for TT is 0.985 (98.5%), and in the case heterozygous for TA is 0.015 (1.5%). Our results suggest that genetic variations in afamin might be associated with male infertility. These findings could significantly enhance our understanding of the molecular genetic causes of infertility.

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

Fig. 1
Fig. 2

Similar content being viewed by others

Change history

References

  1. Lichenstein HS, Lyons DE, Wurfel MM. Afamin is a new member of the albumin, α-fetoprotein, and vitamin D-binding protein gene family. J Biol Chem. 1994;269:18149–54.

    Article  CAS  Google Scholar 

  2. Bélange J, Roy D, Allard D. New albumin gene 3′ adjacent to the α1-fetoprotein locus. J Biol Chem. 1994;269:5481–4.

    Article  Google Scholar 

  3. Jerkovic L, Voegele AF, Chwatal S. Afamin is a novel human vitamin E-binding glycoprotein characterization and in vitro expression. J Proteome Res. 2005;4:889–99.

    Article  CAS  Google Scholar 

  4. Voegele AF, Jerkovic L, Wellenzohn B. Characterization of the vitamin E-binding properties of human plasma afamin. Biochemistry. 2002;41:14532–8.

    Article  CAS  Google Scholar 

  5. Angelucci S, Ciavardelli D, Di Giuseppe F. Proteome analysis of human follicular fluid. Biochim Biophys Acta. 2006;1764:1775–85.

    Article  CAS  Google Scholar 

  6. Heiser M, Hutter-Paier B, Jerkovic L, Pfragner R, Windisch M, Becker-Andre M, et al. Vitamin E binding protein afamin protects neuronal cells in vitro. J Neural Transm Suppl. 2002;62:337–45.

    Article  CAS  Google Scholar 

  7. Dieplinger H, Dieplinger B. Afamin–a pleiotropic glycoprotein involved in various disease states. Clin Chim Acta. 2015;15(446):105–10.

  8. Lambrinoudaki IV, Augouela A, Christodoulakos GE, Economou EV, Kaparos G, Kontoravdis A. Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril. 2009;91:46–50.

    Article  CAS  Google Scholar 

  9. Seeber BE, Czech T, Buchner H, Barnhart KT, Seger C, Daxenbichler G, et al. The vitamin E–binding protein afamin is altered significantly in the peritoneal fluid of women with endometriosis. Fertil Steril. 2010;94:2923–6.

    Article  CAS  Google Scholar 

  10. Köninger A, Enekwe A, Mach P, Andrikos D, Schmidt B, Frank M, et al. Afamin: an early predictor of preeclampsia. Arch Gynecol Obstet. 2018;298:1009–16.

    Article  Google Scholar 

  11. Köninger A, Mathan A, Mach P, Frank M, Schmidt B, Schleussner E, et al. Is Afamin a novel biomarker for gestational diabetes mellitus? A pilot study. Reprod Biol Endocrinol. 2018;27:30–8.

    Article  Google Scholar 

  12. Ringman JM, Schulman H, Becker C, Jones T, Bai Y, Immermann F, et al. Proteomic changes in cerebrospinal fluid of presymptomatic and affected persons carrying familial Alzheimer disease mutations. Arch Neurol. 2012;69:96–104.

    Article  Google Scholar 

  13. Rosenling T, Stoop MP, Attali A, Aken H, Suidgeest E, Christin C, et al. Profiling and identification of cerebrospinal fluid proteins in a rat EAE model of multiple sclerosis. J Proteome Res. 2012;11:2048–60.

    Article  CAS  Google Scholar 

  14. Song F, Poljak A, Kochan NA, Raftery M, Brodaty H, Smythe GA, et al. Plasma protein profiling of mild cognitive impairment and Alzheimer's disease using iTRAQ quantitative proteomics. Proteome Sci. 2014;12:5.

    Article  Google Scholar 

  15. Jackson D, Craven RA, Hutson RC. Proteomic profiling identifies afamin as a potential biomarker for ovarian cancer. Clin Cancer Res. 2007;13:7370–9.

    Article  CAS  Google Scholar 

  16. Dieplinger H, Ankerst DP, Burges A. Afamin and apolipoprotein A-IV: novel protein markers for ovarian cancer. Cancer Epidemiol Biomark Prev. 2009;18:1127–33.

    Article  CAS  Google Scholar 

  17. Melmer A, Fineder L, Lamina C. Plasma concentrations of the vitamin E-binding protein afamin are associated with overall and progression-free survival and platinum sensitivity in serous ovarian cancer—a study by the OVCAD consortium. Gynecol Oncol. 2013;128:38–43.

    Article  CAS  Google Scholar 

  18. Chen YT, Chen HW, Domanski D, Smith DS, Liang KH, Wu CC, et al. Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers. J Proteome. 2012;75:3529–45.

    Article  CAS  Google Scholar 

  19. Choi JW, Liu H, Shin DH, Yu GI, Hwang JS, Kim ES, et al. Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients. Proteomics. 2013;13:2361–74.

    Article  CAS  Google Scholar 

  20. Humphries JM, Penno MA, Weiland F, et al. Identification and validation of novel candidate protein biomarkers for the detection of human gastric cancer. Biochim Biophys Acta. 1844;2014:1051–8.

    Google Scholar 

  21. Jeong DH, Kim HK, Prince AE, et al. Plasma proteomic analysis of patients with squamous cell carcinoma of the uterine cervix. J Gynecol Oncol. 2008;19:173–80.

    Article  CAS  Google Scholar 

  22. Wang WK, Tsai CH, Liu YW, Lai CC, Huang CC, Sheen-Chen SM. Afamin expression in breast cancer. Asian J Surg. 2020;43:750–4.

    Article  Google Scholar 

  23. Song HJ, Xue YL, Qiu ZL, Luo QY. Comparative serum proteomic analysis identified afamin as a downregulated protein in papillary thyroid carcinoma patients with non-131I-avid lung metastases. Nucl Med Commun. 2013;34:1196–203.

    Article  CAS  Google Scholar 

  24. Kronenberg F, Kollerits B, Kiechl S, Lamina C, Kedenko L, Meisinger C, et al. Plasma concentrations of afamin are associated with the prevalence and development of metabolic syndrome. Circ Cardiovasc Genet. 2014;7:822–9.

    Article  CAS  Google Scholar 

  25. Kollerits B, Lamina C, Huth C, Marques-Vidal P, Kiechl S, Seppälä I, et al. Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes: a pooled analysis in more than 20,000 individuals. Diabetes Care. 2017;40:1386–93.

    Article  CAS  Google Scholar 

  26. Kaburagi Y, Takahashi E, Kajio H, Yamashita S, Yamamoto-Honda R, Shiga T, et al. Urinary afamin levels are associated with the progression of diabetic nephropathy. Diabetes Res Clin Pract. 2019;147:37–46.

    Article  CAS  Google Scholar 

  27. https://patents.google.com/patent/EP2328605A1/en.

  28. Liu J, Huang X, Cao X, Feng X, Wang X. Serum biomarker analysis in patients with premature ovarian insufficiency. Cytokine. 2020;126:154876.

    Article  CAS  Google Scholar 

  29. World Health Organization. Laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.

    Google Scholar 

  30. Asbaghi O, Sadeghian M, Nazarian B, Sarreshtedari M, Mozaffari-Khosravi H, Maleki V, et al. The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep. 2020;10(1):17234.

    Article  CAS  Google Scholar 

  31. Zhang JG, Nicholls-Grzemski FA, Tirmenstein MA, Fariss MW. Vitamin E succinate protects hepatocytes against the toxic effect of reactive oxygen species generated at mitochondrial complexes i and iii by alkylating agents. Chem Biol Interact. 2001;138(3):267–84.

    Article  CAS  Google Scholar 

  32. Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R. Role of oxidative stress, infection, and inflammation in male infertility. Andrologia. 2018;50:131–6.

    Google Scholar 

  33. Bhardwaj A, Verma A, Majumdar S, Khanduja KL. Status of vitamin E and reduced glutathione in semen of oligozoospermic and azoospermic patients. Asian J Androl. 2000;2(3):225–8.

    CAS  PubMed  Google Scholar 

  34. Al-Azemi MK, Omu AE, Fatinikun T, Mannazhath N, Abraham S. Factors contributing to gender differences in serum retinol and alpha-tocopherol in infertile couples. Reprod BioMed Online. 2009;19(4):583–90.

    Article  CAS  Google Scholar 

  35. Zerbinati C, Caponecchia L, Fiori C, Sebastianelli A, Salacone P, Ciacciarelli M. Iuliano L alpha- and gamma-tocopherol levels in human semen and their potential functional implications. Andrologia. 2020;52:56–62.

    Article  Google Scholar 

  36. Benedetti S, Tagliamonte MC, Catalani S, Primiterra M, Canestrari F, De Stefani S, et al. Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod BioMed Online. 2012;25(3):300–6.

    Article  CAS  Google Scholar 

  37. Koninger A, Edimiris P, Koch L, Enekwe A, Lamina C, Kasimir-Bauer S, et al. Serum concentrations of afamin are elevated in patients with polycystic ovary syndrome. Endocr Connect. 2014;3(3):120–6.

    Article  Google Scholar 

  38. O’Flynn O’Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93:1–12.

    Article  Google Scholar 

  39. Liu J, Walp ER, May CL. Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass. Islets. 2012;4(3):199–206.

    Article  Google Scholar 

Download references

Funding

This work was supported by the Tambre Foundation.

Author information

Authors and Affiliations

  1. International Assisted Reproduction Unit, Madrid, IERA Foundation, Madrid, Avenida General Perón 20, 28020, Madrid, Spain

    Rocio Nuñez-Calonge & Pedro Caballero Peregrín

  2. Tambre Clinic Madrid, Madrid, Spain

    Susana Cortes

  3. University “Alfonso X el Sabio”, Madrid, Spain

    Luis Miguel Gutierrez Gonzalez

  4. Galicia Sur Health Research Institute, Vigo, Spain

    Roman Kireev

Authors
  1. Rocio Nuñez-Calonge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susana Cortes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pedro Caballero Peregrín
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luis Miguel Gutierrez Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roman Kireev
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RNC contributed to the conception and design of the study, data analysis, interpretation of the data, and drafting of the manuscript. SC was responsible for the collection of sperm samples and aided in drafting the manuscript. PCP was responsible for data analysis and interpretation. LMGG and RK were responsible for the afamin measurements, DNA extraction, and genotyping. RK was responsible for revision and final approval of the manuscript.

Corresponding author

Correspondence to Rocio Nuñez-Calonge.

Ethics declarations

The study was allowed by ethical committee: Hospital de la Princesa, Madrid, approval n° PI-827.

Conflict of Interest

The authors declare they have no competing interests.

Additional information

Publisher’s Note

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

This article was updated to correct errors in Table 1 and References 7 and 27.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nuñez-Calonge, R., Cortes, S., Caballero Peregrín, P. et al. Seminal Plasma and Serum Afamin Levels Are Associated with Infertility in Men with Oligoasthenoteratozoospermia. Reprod. Sci. 28, 1498–1506 (2021). https://doi.org/10.1007/s43032-020-00436-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-020-00436-8

Keywords

Search

Navigation