Skip to main content

Advertisement

SpringerLink
Log in

Association of follicle-stimulating hormone receptor single nucleotide polymorphisms with fertility in Greek men

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background and objective

Although several epidemiological studies have been conducted, the impact of follicle-stimulating hormone receptor (FSHR) polymorphisms on male infertility remains unclear. The aim of this study was to investigate the prevalence of specific FSHR single nucleotide polymorphisms (SNPs) in the Greek population and associate the latter with the clinical phenotype.

Patients and methods

We enrolled 96 subjects: men with idiopathic non-obstructive azoospermia (n = 78) were compared with a control group of fertile men (n = 18) for SNPs in FSHR positions c.-29, c.566, c.919, and c.2039. The SNP in position 566 (c.566C > T) was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the other three SNPs (c.-29G > A, c.919A > G, c.2039A > G) with single-strand conformation polymorphism (SSCP); all of them were validated with DNA sequence.

Results

No polymorphisms were detected in positions c.-29 and c.919 (c.-29G > A, c.919A > G). The heterozygous SNP (AG) at position 2039 was associated with different size of the right testis (p = 0.008). There was no association between the c.566C > T SNPs polymorphism and hormonal or semen parameters. The combination SNP 2039 AA with 566 CT revealed significant association with FSH and LH concentrations.

Conclusions

FSHR SNPs at positions c.-29, c.566, c.919, and c.2039 (c.-29G > A, c.566C > T, c.919A > G, c.2039A > G) do not appear to play specific roles in male infertility. Larger studies are needed to confirm these results.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. de Kretser DM, Baker HW (1999) Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 84:3443–3450

    PubMed  Google Scholar 

  2. Pieri Pde C, Pereira DH, Glina S et al (2002) A cost-effective screening test for detecting AZF microdeletions on the human Y chromosome. Genet Test 6:185–194

    Article  PubMed  Google Scholar 

  3. Ferlin A, Vinanzi C, Garolla A et al (2006) Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin Endocrinol 65:606–610

    Article  CAS  Google Scholar 

  4. Chappel SC, Howles C (1991) Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Hum Reprod 6:1206–1212

    Article  CAS  PubMed  Google Scholar 

  5. Krishnamurthy H, Danilovich N, Morales CR et al (2000) Qualitative and quantitative decline in spermatogenesis of the follicle-stimulating hormone receptor knockout (FORKO) mouse. Biol Reprod 62:1146–1159

    Article  CAS  PubMed  Google Scholar 

  6. Fan QR, Hendrickson WA (2005) Structure of human follicle-stimulating hormone in complex with its receptor. Nature 433(7023):269–277

    Article  CAS  PubMed  Google Scholar 

  7. Minegishi T, Nakamura K, Takakura Y et al (1991) Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun 175:1125–1130

    Article  CAS  PubMed  Google Scholar 

  8. Gromoll J, Simoni M (2005) Genetic complexity of FSH receptor function. Trends Endocrinol Metab 16:368–373

    Article  CAS  PubMed  Google Scholar 

  9. Wunsch A, Ahda Y, Banaz-Yaşar F et al (2005) Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertil Steril 84:446–453

    Article  CAS  PubMed  Google Scholar 

  10. Tapanainen JS, Aittomaki K, Min J et al (1997) Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat Genet 15:205–206

    Article  CAS  PubMed  Google Scholar 

  11. Ahda Y, Gromoll J, Wunsch A et al (2005) Follicle-stimulating hormone receptor gene haplotype distribution in normozoospermic and azoospermic men. J Androl 26:494–499

    Article  CAS  PubMed  Google Scholar 

  12. Asatiani K, Gromoll J, Eckardstein SV et al (2002) Distribution and function of FSH receptor genetic variants in normal men. Andrologia 34:172–176

    Article  CAS  PubMed  Google Scholar 

  13. Balkan M, Gedik A, Akkoc H et al (2010) FSHR single nucleotide polymorphism frequencies in proven fathers and infertile men in Southeast Turkey. J Biomed Biotechnol 2010:640318

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ghirelli-Filho M, Peluso C, Christofolini DM et al (2012) Variants in follicle-stimulating hormone receptor gene in infertile Brazilian men and the correlation to FSH serum levels and sperm count. Reprod Sci 19:733–739

    Article  CAS  PubMed  Google Scholar 

  15. Grigorova M, Punab M, Poolamets O et al (2013) Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume. Andrology 1:293–300

    Article  CAS  PubMed  Google Scholar 

  16. Lazaros L, Xita N, Takenaka A et al (2013) Synergistic effect of follicle-stimulating hormone receptor and androgen receptor gene variants on semen quality. Andrologia 45:339–344

    Article  CAS  PubMed  Google Scholar 

  17. Lend AK, Belousova A, Haller-Kikkatalo K et al (2010) Follicle-stimulating hormone receptor gene haplotypes and male infertility in estonian population and meta-analysis. Syst Biol Reprod Med 56:84–90

    Article  CAS  PubMed  Google Scholar 

  18. Li Y, Gu A, Yang H et al (2011) FSH receptor gene polymorphisms in fertile and infertile Han-Chinese males. Clin Chim Acta 412:1048–1052

    Article  CAS  PubMed  Google Scholar 

  19. Lindgren I, Giwercman A, Axelsson J et al (2012) Association between follicle-stimulating hormone receptor polymorphisms and reproductive parameters in young men from the general population. Pharmacogenet Genomics 22:667–672

    Article  CAS  PubMed  Google Scholar 

  20. Pengo M, Ferlin A, Arredi B et al (2006) FSH receptor gene polymorphisms in fertile and infertile Italian men. Reprod Biomed Online 13:795–800

    Article  PubMed  Google Scholar 

  21. Safarinejad MR, Shafiei N, Safarinejad S (2011) Evaluating the role of the FSH receptor gene Thr307-Ala and Asn680-Ser polymorphisms in male infertility and their association with semen quality and reproductive hormones. BJU Int 108:E117–E125

    Article  PubMed  Google Scholar 

  22. Shimoda C, Koh E, Yamamoto K et al (2009) Single nucleotide polymorphism analysis of the follicle-stimulating hormone (FSH) receptor in Japanese with male infertility: identification of codon combination with heterozygous variations of the two discrete FSH receptor gene. Endocr J 56:859–865

    Article  CAS  PubMed  Google Scholar 

  23. Simoni M, Gromoll J, Höppner W et al (1999) Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J Clin Endocrinol Metab 84:751–755

    CAS  PubMed  Google Scholar 

  24. Song GJ, Park YS, Lee HS et al (2001) Mutation screening of the FSH receptor gene in infertile men. Mol Cells 12:292–297

    CAS  PubMed  Google Scholar 

  25. Tüttelmann F, Laan M, Grigorova M et al (2012) Combined effects of the variants FSHB– 211G > T and FSHR 2039A > G on male reproductive parameters. J Clin Endocrinol Metab 97:3639–3647

    Article  PubMed  Google Scholar 

  26. Wu W, Cai H, Sun H et al (2012) Follicle stimulating hormone receptor G-29A, 919A > G, 2039A > G polymorphism and the risk of male infertility: a meta-analysis. Gene 505:388–392

    Article  CAS  PubMed  Google Scholar 

  27. Wu XQ, Xu SM, Wang YQ et al (2015) FSHR gene Thr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis. Genet Mol Res 14:5592–5601

    Article  CAS  PubMed  Google Scholar 

  28. Zalata AA, Hassan AH, Nada HA et al (2008) Follicle-stimulating hormone receptor polymorphism and seminal anti-Mullerian hormone in fertile and infertile men. Andrologia 40:392–397

    Article  CAS  PubMed  Google Scholar 

  29. Pilatz A, Rusz A, Wagenlehner F, Weidner W, Altinkilic B (2013) Reference values for testicular volume, epididymal head size and peak systolic velocity of the testicular artery in adult males measured by ultrasonography. Ultraschall Med 34(4):349–354

    CAS  PubMed  Google Scholar 

  30. Goede J, Hack WW, Sijstermans K, van der Voort-Doedens LM, Van der Ploeg T, Meij-de Vries A et al (2011) Normative values for testicular volume measured by ultrasonography in a normal population from infancy to adolescence. Horm Res Paediatr 76(1):56–64

    Article  CAS  PubMed  Google Scholar 

  31. Lotti F, Maggi M (2015) Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update 21(1):56–83

    Article  PubMed  Google Scholar 

  32. Tournaye H, Verheyen G, Nagy P et al (1997) Are there any predictive factors for successful testicular sperm recovery in azoospermic patients? Hum Reprod 12:80–86

    Article  CAS  PubMed  Google Scholar 

  33. Abdel RA, Garaffa G, Rushwan N et al (2013) Testicular histopathology as a predictor of a positive sperm retrieval in men with non-obstructive azoospermia. BJU Int 111:492–499

    Article  Google Scholar 

  34. Tüttelmann F, Rajpert-De Meyts E, Nieschlag E, Simoni M (2007) Gene polymorphisms and male infertility - a meta-analysis and literature review. Reprod Biomed Online 15:643–658

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Physiology, Faculty of Health Sciences, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    D. Tsitlakidis & A. Kritis

  2. Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    D. Tsitlakidis, D. G. Goulis & I. Papadimas

  3. Diabetologie/Endokrinologie, III Medizinische Klinik, University Klinikum, Jena, Germany

    D. Tsitlakidis

  4. Laboratory of Biology, Faculty of Health Sciences, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    T. Katopodi

Authors
  1. D. Tsitlakidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Katopodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. G. Goulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Papadimas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Kritis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Tsitlakidis.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Aristotle University of Thessaloniki and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsitlakidis, D., Katopodi, T., Goulis, D.G. et al. Association of follicle-stimulating hormone receptor single nucleotide polymorphisms with fertility in Greek men. J Endocrinol Invest 40, 721–726 (2017). https://doi.org/10.1007/s40618-017-0637-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0637-7

Keywords

Search

Navigation