Abstract
Purpose:
Infertility affects 10–15 % of the population, of which, approximately 40 % is due to male etiology consisting primarily of low sperm count (oligozoospermia) and/or abnormal sperm motility (asthenozoospermia). It has been demonstrated that mtDNA base substitutions can greatly influence semen quality.
Methods:
In the present study we performed a systematic sequence analysis of the mitochondrial cytochrome oxidase III (COIII) gene in 31 asthenozoospermic infertile men in comparaison to normozoospermic infertile men (n=33) and fertile men (n=150) from Tunisian population.
Results:
A novel m.9588G>A mutation was found in the mtDNA sperm’s in all asthenozoospermic patients and was absent in the normozoospermic and in fertile men. The m.9588G>A mutation substitutes a highly conserved Glutamate at position 128 to Lysine. In addition, PolyPhen-2 analysis predicted that this variant is “probably damaging”.
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References
Følgero T, Bertheussen K, Lindal S, Torbergsen T, Oian P. Mitochondrial disease and reduced sperm motility. Hum Reprod. 1993;8:1863–8.
Wallace DC. Mitochondrial DNA, variation in human evolution, degenerative disease, and aging. Am J Hum Genet. 1995;57:201–23.
Clayton DA, Doda JN, Friedberg EC. The absence of a pyrimidine dimer repair mechanism in mammalian mitochondria. Proc Natl Acad Sci U S A. 1974;71:2777–81.
Fukunaga M, Yielding K. Fate during cell growth of yeast mitochondrial and nuclear DNA after photolytic attachment of the monoazide analog of ethidium bromide. Biochem Biophys Res Commun. 1979;90:582–6.
Richter C, Park JW, Ames BN. Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci U S A. 1988;85:6465–7.
Nagley P, Zhang C, Martinus RD, Vaillant F, Linnane AW. Mitochondrial DNA mutation and human aging: molecular biology, bioenergetics, and redox therapy. In: DiMauro 1993
Johns DR. Mitochondrial DNA, and disease. N Engl J Med. 1995;333:638–44.
Mitchell JA, Nelson L, Hafez E. Motility of spermatozoa. In: Hafez ESE, editor. Human semen and fertility regulation in men. St. Louis: C. V. Mosby; 1976. p. 83–106.
Kao SH, Chao HT, Wei YH. Mitochondrial deoxyribonucleic acid 4977-bp deletion is associated with diminished fertility and motility of human sperm. Biol Reprod. 1995;52:729–36.
Frank SA, Hurst LD. Mitochondria and male disease. Nature. Enriquez: Guan MX; 1996. p. 224–383.
St. John JC, Cooke ID, Barratt CL. Mitochondrial mutations and male infertility. Nat Med. 1997;3:124–5.
Zeviani M, Antozzi C. Mitochondrial disorders. Mol Hum Reprod. 1997;3:133–48.
Ruiz-Pesini E, Lapena A, Diez-Sanchez C, Perez-Martos A, Enriquez J, Diaz M, et al. Human mitochondrial DNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet. 2000;67:682–96 (in this issue).
Zamboni L. Physiology and pathophysiology of the human spermatozoon: the role of electron microscopy. J Electron Microscopy Technique. 1991;17:412–36.
Oates R. Immotile cilia syndromes. Paper presented at a conference of the American Society of Reproductive Medicine: Male Reproduction—Basic, Genetic, and Clinical Information for the Next Millennium, San Francisco, 1998; October 3–4.
Folgero T, Bertheussen K, Lindal S, Tobergsen T, Oian P. Mitochondrial disease and reduced sperm motility. Hum Reprod. 1993;8:1863–8.
Lestienne P, Reynier P, Chretien MF, Penisson-Besnier I, Malthièry Y, Rohmer V. Oligoasthenospermia associated with multiple mitochondrial DNA rearrangements. Mol Hum Reprod. 1997;3:811–4.
Kao SH, Chao HT, Wei YH. Multiple deletions of mitochondrial DNA are associated with the decline of motility and fertility of human spermatozoa. Mol Hum Reprod. 1998;4:657–66.
World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical interaction. 3rd ed. Cambridge, United Kingdom: Cambridge University Press; 1992.
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.
Pereira L, Goncalves J, Bandelt HJ. Mutation C11994T in the mitochondrial ND4 gene is not a cause of low sperm motility in Portugal. Fertil Steril. 2008;89:738–41.
Spiropoulos J, Turnbull DM, Chinnery PF. Can mitochondrial DNA mutations cause sperm dysfunction? Mol Hum Reprod. 2002;8:719–21.
Kumar R, Venkatesh S, Kumar M, Tanwar M, Shamsi MB, Kumar R. et al. Oxidative stress and sperm mitochondrial DNA mutation in idiopathic oligoasthenozoospermic (OA) infertile men. Indian J Biochem Biophys. (2009) (in press).
Thangaraj K, Joshi MB, Reddy AG, Rasalkar AA, Singh L. Sperm mitochondrial mutations as a cause of low sperm motility. J Androl. 2003;24:388–92.
Güney AI, Javadova D, Kırac D, Ulucan K, Koc G, Ergec D, et al. Detection of Y chromosome microdeletions and mitochondrial DNA mutations in male infertility patients. GRM. 2012;1525:1676–5680.
Acknowledgments
We thank the patient and their family for their cooperation in the present study. This work was supported by The Ministry of the Higher Education and the Scientific Research in Tunisia.
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The authors declare that they have no competing interests.
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A systematic sequence analysis of the mitochondrial (COIII) gene have been studied in 64 Tunisian infertile men in order to assess the incidence of mtDNA base substitutions; that can greatly influence semen quality.
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Baklouti-Gargouri, S., Ghorbel, M., Ben Mahmoud, A. et al. Identification of a novel m.9588G > A missense mutation in the mitochondrial COIII gene in asthenozoospermic Tunisian infertile men. J Assist Reprod Genet 31, 595–600 (2014). https://doi.org/10.1007/s10815-014-0187-2
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DOI: https://doi.org/10.1007/s10815-014-0187-2