Original Article
 

The Relationship between HLA-G Gene Polymorphisms and Repeated Implantation Failure in Infertile Couples Undergoing Assisted Reproductive Technique

Abstract

HLA-G is a tolerogenic molecule that expresses in cytotrophoblast cells and plays an important role in immune response suppression in maternal decidua. Interactions between the extracellular domains of the HLA-G protein with cell receptors of the immune system are well-known.This  study  investigated  the  association  between  HLA-G  gene  polymorphism  with repeated implantation failure (RIF). We used PCR followed by the sequencing technique for exons 2, 3, and 4, as well as intron 2 of the HLA-G gene in 100 couples with histories of two or more failed assisted reproductive technique (ART) attempts. The data were compared with the results of our previous study.The results  indicated that  some alleles  of the  HLA-G gene  such as:  0106,  010106, 01010106 and 0105N (null) alleles were significantly higher in the patient group compared to the control group (p<0.05). There were higher SNPs at the +482 T/C and +506  -/C positions in failed ART couples compared to controls (p=0.03; p=0.01, respectively).HLA-G gene polymorphisms do not clearly affect the risk for implantation failure in most couples who undergo ART. However allelic variations, particularly in exons 3 and 4, and intron 2 of the HLA-G gene can lead to ART failure in human embryos.

1. Tan BK, Vandekerckhove P, Kennedy R, Keay SD. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG 2005;112(6):773-80.

2. Scott L. Embryological strategies for overcoming recurrent assisted reproductive technology treatment failure. Hum Fertil (Camb) 2002;5(14):206-14.

3. Margalioth EJ1, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET. Hum Reprod 2006; 21(12):3036-43.

4. Simon A, Laufer N. Repeated implantation failure:clinical approach. Fertil Steril 2012; 97(5):1039-43.

5. Choudhury SR, Knapp LA. Human reproductive failure I: immunological factors. Hum Reprod Update 2001; 7(2):113-34.

6. Donadi EA1, Castelli EC, Arnaiz-Villena A, Roger M, Rey D, Moreau P. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cell Mol Life Sci 2011; 68(3):369-95.

7. Hviid TV. HLA-G in human reproduction: aspects of genetics, function and pregnancy complications. Hum Reprod Update 2006; 12(3):209-32.

8. Carosella ED1, Moreau P, Le Maoult J, Le Discorde M, Dausset J, Rouas-Freiss N. HLA-G molecules: from maternal-fetal tolerance to tissue acceptance. Adv Immunol 2003; 81:199-252.

9. Rizzo R1, Vercammen M, van de Velde H, Horn PA, Rebmann V. The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells. Cell Mol Life Sci 2011;68(3): 341-52.

10. Shaikly VR1, Morrison IE, Taranissi M, Noble CV, Withey AD, Cherry RJ, et al. Analysis of HLA-G in maternal plasma, follicular fluid, and preimplantation embryos reveal an asymmetric pattern of expression. J Immunol 2008;180(6):4330-7.

11. Yao YQ, Barlow DH, Sargent IL. Differential expression of alternatively spliced transcripts of HLA-G in human preimplantation embryos and inner cell masses. J Immunol 2005; 175(12): 8379-85.

12. Carosella ED, Moreau P, Lemaoult J, et al. HLA-G:from biology to clinical benefits. Trends Immunol 2008; 29(3):125-32.

13. Carosella ED1, Favier B, Rouas-Freiss N, Moreau P, Lemaoult J. Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood 2008; 111(10):4862-70.

14. Bahri R, Hirsch F, Josse A, Rouas-Freiss N, Bidere N, Vasquez A, et al. Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes. J Immunol 2006; 176(3):1331-9.

15. Lila N, Rouas-Freiss N, Dausset J, Carpentier A, Carosella ED. Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo- proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci U S A 2001;98(21):12150-5.

16. Shiroishi M, Kuroki K, Rasubala L, Tsumoto K, Kumagai I, Kurimoto E, et al. Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d). Proc Natl Acad Sci U S A 2006; 103(44):16412-7.

17. Gao GF, Willcox BE, Wyer JR, Boulter JM, O'Callaghan CA, Maenaka K, et al. Classical and nonclassical class I major histocompatibility complex molecules exhibit subtle conformational differences that affect binding to CD8alphaalpha. J Biol Chem 2000; 275(20):15232-8.

18. Wold AS, Arici A. Natural killer cells and reproductive failure. Curr Opin Obstet Gynecol 2005; 17(3):237-41.

19. Moffett-King A. Natural killer cells and pregnancy.Nat Rev Immunol 2002; 2:656-63.20. Rebmann V, Switala M, Eue I, Grosse-Wilde H.Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART: a German multi-centre study. Hum Reprod 2010;25(7):1691-8.

21. Hviid TV, Hylenius S, Lindhard A, Christiansen OB. Association between human leukocyte antigen- G genotype and success of in vitro fertilization and pregnancy outcome. Tissue antigens 2004;64(1):66-9.

22. Pfeiffer KA, Fimmers R, Engels G, van der Ven H, van der Ven K. The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion. Mol Hum Reprod 2001; 7:373-8.

23. Ober C, Aldrich CL, Chervoneva I, Billstrand C, Rahimov F, Gray HL, et al. Variation in the HLA-G promoter region influences miscarriage rates. Am J Hum Genet 2003; 72(6):1425-35.

24. Kuroshli Z, Gourabi H, Bazrgar M, Sanati MH, Bahraminejad E, Anisi K. HLA-G allele and Haplotype Frequencies in a Healthy Population of Iran. Iran J Allergy Asthma Immunol 2014;13(3):207-13.

25. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16(3):1215.

26. Rebmann V, van der Ven K, Pässler M, Pfeiffer K, Krebs D, Grosse-Wilde H. Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue antigens 2001; 57(1):15-21.

27. Coulam CB, Moore SB, O'Fallon W. Investigating unexplained infertility. Am J Obstet Gynecol 1988;158(6 Pt 1):1374-81.

28. Hunt JS, Langat DK, McIntire RH, et al. The role of HLA-G in human pregnancy. Reprod Biol Endocrinol 2006; ( 4 Suppl 1):S10.

29. Sipak-Szmigiel O, Ronin-Walknowska E, Cybulski C, Plonka T, Lubiński J. Antigens HLA-G, sHLA- G and sHLA- class I in reproductive failure. Folia Histochem Cytobiol 2007; (45 Suppl 1):S137-41.

30. Gobin SJ, van Zutphen M, Woltman AM, van den Elsen PJ. Transactivation of classical and nonclassical HLA class I genes through the IFN- stimulated response element. J Immunol 1999;163(3):1428-34.

31. Hviid TV1, Hylenius S, Rørbye C, Nielsen LG.HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. Immunogenetics 2003;55(2):63-79.

32. Castelli EC, Mendes-Junior CT, Deghaide NH, de Albuquerque RS, Muniz YC, Simões RT, et al. The genetic structure of 3'untranslated region of the HLA-G gene: polymorphisms and haplotypes. Genes Immun 2010; 11(2):134-41.

33. Castelli EC, Moreau P, Oya e Chiromatzo A, Mendes-Junior CT, Veiga-Castelli LC, Yaghi L, et al. In silico analysis of microRNAS targeting the HLA-G 3' untranslated region alleles and haplotypes. Hum Immunol 2009; 70(12):1020-5.

Files
IssueVol 14, No 5 (2015) QRcode
SectionOriginal Article(s)
Keywords
ART HLA-G polymorphism Implantation RIF

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Kuroshli Z, Gourabi H, Bazrgar M, Sanati MH, Zamani Esteki M. The Relationship between HLA-G Gene Polymorphisms and Repeated Implantation Failure in Infertile Couples Undergoing Assisted Reproductive Technique. Iran J Allergy Asthma Immunol. 2015;14(5):535-542.