Reproductive BioMedicine Online
Volume 19, Issue 5 , Pages 685-694 , November 2009

Cystic fibrosis transmembrane conductance regulator mutations in azoospermic and oligospermic men and their partners

  • Sabina Gallati

      Affiliations

    • Division of Human Genetics, Departments of Paediatrics and Clinical Research, Inselspital, University of Berne, CH-3010 Berne, Switzerland
    • Corresponding Author InformationCorrespondence:
  • ,
  • Simone Hess

      Affiliations

    • Division of Human Genetics, Departments of Paediatrics and Clinical Research, Inselspital, University of Berne, CH-3010 Berne, Switzerland
  • ,
  • Dorothea Galié-Wunder

      Affiliations

    • Division of Gynaecological Endocrinology and Reproductive Medicine, Inselspital, University of Berne, CH-3010 Berne, Switzerland
  • ,
  • Elisabeth Berger-Menz

      Affiliations

    • Division of Obstetrics and Gynaecology, Lindenhofspital, CH-3001 Berne, Switzerland
  • ,
  • Dominik Böhlen

      Affiliations

    • Division of Urology, Clinic Beau-Site, CH-3013 Berne, Switzerland

Received 3 November 2008 ,Revised 20 January 2009 ,Accepted 1 June 2009.

References 

  1. Anguiano A, Oates RD, Amos JA, et al. Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis. Journal of the American Medical Association. 1992;267:1794–1797
  2. Blau H, Freud E, Mussaffi H, et al. Urogenital abnormalities in male children with cystic fibrosis. Archives of Disease in Childhood. 2002;87:135–138
  3. Boucher D, Creveaux I, Grizard G, et al. Screening for cystic fibrosis transmembrane conductance regulator gene mutations in men included in an intracytoplasmic sperm injection programme. Molecular Human Reproduction. 1999;5:587–593
  4. Buratti E, Dork T, Zuccato E, et al. Nuclear factor TDP-43 and SR proteins promote in-vitro and in-vivo CFTR exon 9 skipping. European Molecular Biology Organization Journal. 2001;20:1774–1784
  5. Burrello N, Calogero AE, De Palma A, et al. Chromosome analysis of epididymal and testicular spermatozoa in patients with azoospermia. European Journal of Human Genetics. 2002;10:362–366
  6. Casals T, Bassas L, Egozcue S, et al. Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens. Human Reproduction. 2000;15:1476–1483
  7. Chillon M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. New England Journal of Medicine. 1995;332:1475–1480
  8. Claustres M. Molecular pathology of the CFTR locus in male infertility. Reproductive BioMedicine Online. 2005;10:14–41
  9. Claustres M, Guittard C, Bozon D, et al. Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France. Human Mutation. 2000;16:143–156
  10. Cuppens H, Cassiman JJ. CFTR mutations and polymorphisms in male infertility. International Journal of Andrology. 2004;27:251–256
  11. Cuppens H, Lin W, Jaspers M, et al. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. Journal of Clinical Investigation. 1998;101:487–496
  12. de Meeus A, Guittard C, Desgeorges M, et al. Linkage disequilibrium between the M470V variant and the IVS8 polyT alleles of the CFTR gene in CBAVD. Journal of Medical Genetics. 1998;35:594–596
  13. Disset A, Michot C, Harris A, et al. A T3 allele in the CFTR gene exacerbates exon 9 skipping in vas deferens and epididymal cell lines and is associated with congenital bilateral absence of vas deferens (CBAVD). Human Mutation. 2005;25:72–81
  14. Dohle GR, Halley DJ, Van Hemel JO, et al. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia. Human Reproduction. 2002;17:13–16
  15. Douet-Guilbert N, Bris MJ, Amice V, et al. Interchromosomal effect in sperm of males with translocations: report of 6 cases and review of the literature. International Journal of Andrology. 2005;28:372–379
  16. Faddy MJ, Silber SJ, Gosden RG. Intra-cytoplasmic sperm injection and infertility. Nature Genetics. 2001;29:131
  17. Foresta C, Ferlin A, Gianaroli L, et al. Guidelines for the appropriate use of genetic tests in infertile couples. European Journal of Human Genetics. 2002;10:303–312
  18. Grangeia A, Sa R, Carvalho F, et al. Molecular characterization of the cystic fibrosis transmembrane conductance regulator gene in congenital absence of the vas deferens. Genetics in Medicine. 2007;9:163–172
  19. Groman JD, Hefferon TW, Casals T, et al. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. American Journal of Human Genetics. 2004;74:176–179
  20. Healy DL, Trounson AO, Andersen AN. Female infertility: causes and treatment. Lancet. 1994;343:1539–1544
  21. Hefferon TW, Broackes-Carter FC, Harris A, et al. Atypical 5′ splice sites cause CFTR exon 9 to be vulnerable to skipping. American Journal of Human Genetics. 2002;71:294–303
  22. Hellani A, Al-Hassan S, Iqbal M, et al. Y chromosome microdeletions in infertile men with idiopathic oligo- or azoospermia. Journal of Experimental and Clinical Assisted Reproduction. 2006;3:1
  23. Jarvi K, Zielenski J, Wilschanski M, et al. Cystic fibrosis transmembrane conductance regulator and obstructive azoospermia. Lancet. 1995;345:1578
  24. Keymolen K, Goossens V, De Rycke M, et al. Clinical outcome of preimplantation genetic diagnosis for cystic fibrosis: the Brussels’ experience. European Journal of Human Genetics. 2007;15:752–758
  25. Kihaile PE, Yasui A, Shuto Y. Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin. Journal of Experimental and Clinical Assisted Reproduction. 2005;2:9
  26. Larriba S, Bonache S, Sarquella J, et al. Molecular evaluation of CFTR sequence variants in male infertility of testicular origin. International Journal of Andrology. 2005;28:284–290
  27. Liechti-Gallati S, Schneider V, Neeser D, et al. Two buffer PAGE system-based SSCP/HD analysis: a general protocol for rapid and sensitive mutation screening in cystic fibrosis and any other human genetic disease. European Journal of Human Genetics. 1999;7:590–598
  28. Maeda Y, Shiratsuchi A, Namiki M, et al. Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Cell Death and Differentiation. 2002;9:742–749
  29. Mak V, Zielenski J, Tsui LC, et al. Cystic fibrosis gene mutations and infertile men with primary testicular failure. Human Reproduction. 2000;15:436–439
  30. Mak V, Zielenski J, Tsui LC, et al. Proportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia. Journal of the American Medical Association. 1999;281:2217–2224
  31. Mau-Holzmann UA. Somatic chromosomal abnormalities in infertile men and women. Cytogenetic and Genome Research. 2005;111:317–336
  32. Mennicke K, Klingenberg RD, Bals-Pratsch M, et al. Rational approach to genetic testing of cystic fibrosis (CF) in infertile men. Andrologia. 2005;37:1–9
  33. Mickle J, Milunsky A, Amos JA, et al. Congenital unilateral absence of the vas deferens: a heterogeneous disorder with two distinct subpopulations based upon aetiology and mutational status of the cystic fibrosis gene. Human Reproduction. 1995;10:1728–1735
  34. Pagani F, Buratti E, Stuani C, et al. Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element. Journal of Biological Chemistry. 2000;275:21041–21047
  35. Pallares-Ruiz N, Carles S, Des Georges M, et al. Complete mutational screening of the cystic fibrosis transmembrane conductance regulator gene: cystic fibrosis mutations are not involved in healthy men with reduced sperm quality. Human Reproduction. 1999;14:3035–3040
  36. Patrizio P, Salameh WA. Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in normal and pathological adult human epididymis. Journal of Reproduction and Fertility Supplement. 1998;53:261–270
  37. Ratbi I, Legendre M, Niel F, et al. Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Human Reproduction. 2007;22:1285–1291
  38. Ravnik-Glavac M, Svetina N, Zorn B, et al. Involvement of CFTR gene alterations in obstructive and nonobstructive infertility in men. Genetic Testing. 2001;5:243–247
  39. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989;245:1066–1073
  40. Stuppia L, Antonucci I, Binni F, et al. Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs. European Journal of Human Genetics. 2005;13:959–964
  41. Tamburino L, Guglielmino A, Venti E, et al. Molecular analysis of mutations and polymorphisms in the CFTR gene in male infertility. Reproductive BioMedicine Online. 2008;17:27–35
  42. Trezise AE, Linder CC, Grieger D, et al. CFTR expression is regulated during both the cycle of the seminiferous epithelium and the oestrous cycle of rodents. Nature Genetics. 1993;3:157–164
  43. van der Ven K, Messer L, van der Ven H, et al. Cystic fibrosis mutation screening in healthy men with reduced sperm quality. Human Reproduction. 1996;11:513–517
  44. Wang X, Sharma RK, Sikka SC, et al. Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility. Fertility and Sterility. 2003;80:531–535
  45. Xu WM, Shi QX, Chen WY, et al. Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing capacity and male fertility. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:9816–9821

 Sabina Gallati graduated in Biology and Genetics from the University of Berne. She has undertaken postdoctoral research and training in molecular genetics and forensics in London (UK), Würzburg (Germany), Boston (USA) and Quantico (USA) and has specialised in Medical Genetic Analysis. In 2003, she became Professor of Human Genetics and Head of the Division of Human Genetics at the Medical Faculty of the University of Berne. Her main research interests are genetic mechanisms in Cystic Fibrosis and CFTR-related disorders, hereditary haemochromatosis and mitochondriopathies. Dr Sabina Gallati

PII: S1472-6483(09)00066-2

doi: 10.1016/j.rbmo.2009.09.002

Reproductive BioMedicine Online
Volume 19, Issue 5 , Pages 685-694 , November 2009