Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 4, pp 505–510 | Cite as

The impact of RABL2B gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects

  • Seyedeh Hanieh Hosseini
  • Mohammad Ali Sadighi Gilani
  • Anahita Mohseni Meybodi
  • Marjan Sabbaghian
Genetics

Abstract

Purpose

Male infertility is a multifactorial disorder with impressively genetic basis; besides, sperm abnormalities are the cause of numerous cases of male infertility. In this study, we evaluated the genetic variants in exons 4 and 5 and their intron-exon boundaries in RABL2B gene in infertile men with oligoasthenoteratozoospermia (OAT) and immotile short tail sperm (ISTS) defects to define if there is any association between these variants and human male infertility.

Methods

To this purpose, DNA was extracted from peripheral blood and after PCR reaction and sequencing, the results of sequenced segments were analyzed. In the present study, 30 infertile men with ISTS defect and 30 oligoasthenoteratozoospermic infertile men were recruited. All men were of Iranian origin and it took 3 years to collect patient’s samples with ISTS defect.

Results

As a result, the 50776482 delC intronic variant (rs144944885) was identified in five patients with oligoasthenoteratozoospermia defect and one patient with ISTS defect in heterozygote form. This variant was not identified in controls. The allelic frequency of the 50776482 delC variant was significantly statistically higher in oligoasthenoteratozoospermic infertile men (p < 0.05). Bioinformatics studies suggested that the 50776482 delC allele would modify the splicing of RABL2B pre-mRNA. In addition, we identified a new genetic variant in RABL2B gene.

Conclusions

According to the present study, 50776482 delC allele in the RABL2B gene could be a risk factor in Iranian infertile men with oligoasthenoteratozoospermia defect, but more genetic studies are required to understand the accurate role of this variant in pathogenesis of human male infertility.

Keywords

Immotile short tail sperm Oligoasthenoteratozoospermia RABL2B gene Male infertility 

Notes

Acknowledgements

We thank Amir Amiri-Yekta and Sajjad Sarikhan for kindly helping during the study. Also, we appreciate all patients who cooperated in this research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by Royan Institute funds.

References

  1. 1.
    Rowe P, Comhaire F, Hargreave T, Mellows H. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge: Press Syndicate of the University of Cambridge; 1993.Google Scholar
  2. 2.
    Jamsai D, Lo JC, et al. Genetic variants in the RABL2A gene in fertile and oligoasthenospermic infertile men. Fertil Steril. 2014;102(1):223–9.CrossRefPubMedGoogle Scholar
  3. 3.
    O’Brien KLF, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93(1):1–12.CrossRefGoogle Scholar
  4. 4.
    Chemes HE. Phenotypes of sperm pathology: genetic and acquired forms in infertile men. J Androl. 2000;21(6):799–808.PubMedGoogle Scholar
  5. 5.
    Ben Khelifa M, Coutton C, Zouari R, Karaouzene T, Rendu J, Bidart M, et al. Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Am J Hum Genet. 2014;94(1):95–104.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sironen A, Hansen J, Thomsen B, Andersson M, Vilkki J, Toppari J, et al. Expression of SPEF2 during mouse spermatogenesis and identification of IFT20 as an interacting protein. Biol Reprod. 2010;82(3):580–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Sironen A, Thomsen B, Andersson M, Ahola V, Vilkki J. An intronic insertion in KPL2 results in aberrant splicing and causes the immotile short-tail sperm defect in the pig. Proc Natl Acad Sci U S A. 2006;103(13):5006–11.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Sironen A. Molecular genetics of the immotile short tail sperm defect. 2009.Google Scholar
  9. 9.
    Baccetti B, Burrini AG, Capitani S, Collodel G, Moretti E, Piomboni P, et al. Notulae seminologicae. 2. The ‘short tail’ and ‘stump’ defect in human spermatozoa. Andrologia. 1993;25(6):331–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Wei TC, Huang WJ, Lin AT, Chen KK. The role of hormones on semen parameters in patients with idiopathic or varicocele-related oligoasthenoteratozoospermia (OAT) syndrome. J Chin Med Assoc: JCMA. 2013;76(11):624–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Lo JC, Jamsai D, O’Connor AE, Borg C, Clark BJ, Whisstock JC, et al. RAB-like 2 has an essential role in male fertility, sperm intra-flagellar transport, and tail assembly. PLoS Genet. 2012;8(10):e1002969.Google Scholar
  12. 12.
    Wong AC, Shkolny D, Dorman A, Willingham D, Roe BA, McDermid HE. Two novel human RAB genes with near identical sequence each map to a telomere-associated region: the subtelomeric region of 22q13.3 and the ancestral telomere band 2q13. Genomics. 1999;59(3):326–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Chacon-Cortes D, Griffiths LR. Methods for extracting genomic DNA from whole blood samples: current perspectives. J Biorepos Sci Appl Med. 2014;2014(2):1–9.Google Scholar
  14. 14.
    Orengo JP, Cooper TA. Alternative splicing in disease. Adv Exp Med Biol. 2007;623:212–23.CrossRefPubMedGoogle Scholar
  15. 15.
    Dreumont N, Bourgeois CF, Lejeune F, Liu Y, Ehrmann IE, Elliott DJ, et al. Human RBMY regulates germline-specific splicing events by modulating the function of the serine/arginine-rich proteins 9G8 and Tra2-{beta}. J Cell Sci. 2010;123(Pt 1):40–50.CrossRefPubMedGoogle Scholar
  16. 16.
    Tazi J, Bakkour N, Stamm S. Alternative splicing and disease. Biochim Biophys Acta (BBA)-Molecul Basis Dis. 2009;1792(1):14–26.CrossRefGoogle Scholar
  17. 17.
    Cieply B, Carstens RP. Functional roles of alternative splicing factors in human disease. Wiley Interdisciplin Rev: RNA. 2015;6(3):311–26.CrossRefGoogle Scholar
  18. 18.
    Moretti E, Collodel G. Electron microscopy in the study of human sperm pathologies. Translocat. 2012;33:34.Google Scholar
  19. 19.
    Coutton C et al. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update. 2015;21(4):455–85.CrossRefPubMedGoogle Scholar
  20. 20.
    McAlister DA. A comparison of motility and head morphology of sperm using different semen processing methods and three different staining techniques. Stellenbosch: University of Stellenbosch; 2010.Google Scholar
  21. 21.
    Medicine, P.C.o.t.A.S.f.R. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2012;98(2):294–301.CrossRefGoogle Scholar
  22. 22.
    Chemes H et al. Ultrastructural pathology of the sperm flagellum: association between flagellar pathology and fertility prognosis in severely asthenozoospermic men. Hum Reprod. 1998;13(9):2521–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Chemes HE et al. Dysplasia of the fibrous sheath: an ultrastructural defect of human spermatozoa associated with sperm immotility and primary sterility. Fertil Steril. 1987;48(4):664–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Escalier D, David G. Pathology of the cytoskeleton of the human sperm flagellum: axonemal and peri‐axonemal anomalies. Biol Cell. 1984;50(1):37–52.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Seyedeh Hanieh Hosseini
    • 1
  • Mohammad Ali Sadighi Gilani
    • 1
    • 2
  • Anahita Mohseni Meybodi
    • 3
  • Marjan Sabbaghian
    • 1
  1. 1.Department of Andrology, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  2. 2.Department of Urology, Shariati HospitalTehran University of Medical SciencesTehranIran
  3. 3.Department of Genetics, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran

Personalised recommendations