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

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

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.

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References

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  3. O’Brien KLF, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93(1):1–12.

    Article  Google Scholar 

  4. Chemes HE. Phenotypes of sperm pathology: genetic and acquired forms in infertile men. J Androl. 2000;21(6):799–808.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sironen A. Molecular genetics of the immotile short tail sperm defect. 2009.

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

  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.

    Article  CAS  PubMed  Google Scholar 

  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. Orengo JP, Cooper TA. Alternative splicing in disease. Adv Exp Med Biol. 2007;623:212–23.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  16. Tazi J, Bakkour N, Stamm S. Alternative splicing and disease. Biochim Biophys Acta (BBA)-Molecul Basis Dis. 2009;1792(1):14–26.

    Article  CAS  Google Scholar 

  17. Cieply B, Carstens RP. Functional roles of alternative splicing factors in human disease. Wiley Interdisciplin Rev: RNA. 2015;6(3):311–26.

    Article  CAS  Google Scholar 

  18. Moretti E, Collodel G. Electron microscopy in the study of human sperm pathologies. Translocat. 2012;33:34.

    Google Scholar 

  19. Coutton C et al. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update. 2015;21(4):455–85.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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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.

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Author notes

    Authors and Affiliations

    1. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

      Seyedeh Hanieh Hosseini, Mohammad Ali Sadighi Gilani & Marjan Sabbaghian

    2. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

      Mohammad Ali Sadighi Gilani

    3. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

      Anahita Mohseni Meybodi

    Authors
    1. Seyedeh Hanieh Hosseini
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    2. Mohammad Ali Sadighi Gilani
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    3. Anahita Mohseni Meybodi
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    4. Marjan Sabbaghian
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    Corresponding author

    Correspondence to Marjan Sabbaghian.

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    The authors declare that they have no conflict of interest.

    Funding

    This work was supported by Royan Institute funds.

    Additional information

    Capsule This is the first report concerning the role of RABL2B gene in human male infertility. Nucleotide deletion (rs144944885) in RABL2B could alter a splicing factor target site and would be a risk factor in oligoasthenoteratozoospermic infertile men. Also a new genetic variant of RABL2B was identified in this study.

    Anahita Mohseni Meybodi and Marjan Sabbaghian contributed equally to this work.

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    Hosseini, S.H., Sadighi Gilani, M.A., Meybodi, A.M. et al. The impact of RABL2B gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects. J Assist Reprod Genet 34, 505–510 (2017). https://doi.org/10.1007/s10815-016-0863-5

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    • DOI: https://doi.org/10.1007/s10815-016-0863-5

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