Clinical and Experimental Reproductive Medicine

  • 제32권3호
  • /
  • Pages.279-286
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  • 2005
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지

한국 남성 불임환자에서 Protamine 1과 2 유전자의 Single Nucleotide Polymorphism에 관한 연구

Screening of the Single Nucleotide Polymorphisms in the Protamine 1 and 2 Genes of Korean Infertile Men

  • 이형송 (성균관대학교 의과대학 삼성제일병원 생식생물학 및 불임연구실) ;
  • 최혜원 (성균관대학교 의과대학 삼성제일병원 생식생물학 및 불임연구실) ;
  • 박용석 (성균관대학교 의과대학 삼성제일병원 생식생물학 및 불임연구실) ;
  • 서주태 (성균관대학교 의과대학 삼성제일병원 비뇨기과학교실) ;
  • 궁미경 (성균관대학교 의과대학 삼성제일병원 산부인과학교실) ;
  • 전진현 (성균관대학교 의과대학 삼성제일병원 생식생물학 및 불임연구실)
  • Lee, Hyoung-Song (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Hye Won (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Park, Yong-Seog (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Seo, Ju Tae (Department of Urology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Koong, Mi Kyoung (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Jun, Jin Hyun (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine)
  • 발행 : 2005.09.30
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초록

Objective: Although several genetic factors have been associated with defects in human spermatogenesis, the unambiguous causative genes have not been elucidated. The male infertility by haploinsufficiency of PRM1 or PRM2 has been reported in mouse model. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) of PRM1 and PRM2, related to the genotype of Korean infertile men. Methods: Genomic DNAs were extracted from peripheral bloods of infertile men with oligozoospermia or azoospermia, and analyzed using polymerase chain reaction (PCR) and direct sequencing. We carried out the direct sequencing analysis of amplified fragments in PRM1 (557 nucleotides from -42 to 515) and PRM2 (599 nucleotides from 49 to 648) genes, respectively. Results: Three SNPs of coding region in the PRM1 gene was found in the analysis of 130 infertile men. However, the SNPs at a133g (aa 96.9%, ag 3.1% and gg 0.0%), c160a (cc 99.2%, ca 0.8% and aa 0.0%) and c321a (cc 56.9%, ca 35.4% and aa 7.7%) coded the same amino acids, in terms of silence phenotypes. On the other hand, as results of the PRM2 gene sequencing in 164 infertile men, only two SNPs, g398c (gg 62.2%, gc 31.1% and ga 6.7%) and a473c (aa 63.4%, ac 29.9% and cc 6.7%), were identified in the intron of the PRM2 gene. Conclusions: There was no mutation and significant SNPs on PRM1 and PRM2 gene in Korean infertile men. These results suggest that the PRM1 and PRM2 genes are highly conserved and essential for normal fertility of men.

키워드

참고문헌

  1. Cram DS, O'Bryan MK, de Kretser DM. Male infertility genetics-the future. J Androl 2001; 22: 738-46
  2. Wouters-Tyrou D, Martinage A, Chevaillier P, Sautiere P. Nuclear basic proteins in spermiogenesis. Biochimie 1998; 80: 117-28 https://doi.org/10.1016/S0300-9084(98)80018-7
  3. Sassone-Corsi P. Unique chromatin remodeling and transcriptional regulationin spermatogenesis. Science 2002; 296: 2176-8 https://doi.org/10.1126/science.1070963
  4. McKay DJ, Renaux BS, Dixon GH. Rainbow trout protamines. Amino acid sequences of six distinct proteins from a single testis. Eur J Biochem 1986; 158: 361-6 https://doi.org/10.1111/j.1432-1033.1986.tb09759.x
  5. Krawetz SA, Herfort MH, Hamerton JL, Pon RT, Dixon GH. Chromosomal localization and structure of the human Pl protamine gene. Genomics 1989; 5: 639-45 https://doi.org/10.1016/0888-7543(89)90036-0
  6. Reeves RH, Gearhart JD, Hecht NB, Yelick P, Johnson P, O'Brien SJ. Mapping of PRMl to human chromosome 16 and tight linkage of Prm-l and Prm-2 on mouse chromosome 16. J Hered 1989; 80: 442-6
  7. Lee K, Haugen HS, Clegg CH, Braun RE. Premature translation of protamine 1 mRNA causes precocious nuclear condensation and arrests spermatid differentiation in mice. Proc Natl Acad Sci USA 1995; 92: 12451-12455 https://doi.org/10.1073/pnas.92.26.12451
  8. Balhom R, Reed S, Tanphaichitr N. Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. Experientia 1988; 44: 52-5 https://doi.org/10.1007/BF01960243
  9. Belokopytova IA, Kostyleva EI, Tomilin AN, Vorob'ev VI. Human male infertility may be due to a decrease of the protamine P2 content in sperm chromatin. Mol Reprod Dev 1993; 34: 53-7. https://doi.org/10.1002/mrd.1080340109
  10. de Yebra L, Ballesca JL, Vanrell JA, Bassas L, Oliva R. Complete selective absence of protamine P2 in humans. J Biol Chem 1993; 268: 10553-57
  11. Schlicker M, Schnulle V, Schneppel L, Vorob'ev VI, Engel W. Disturbances of nuclear condensation in human spermatozoa: search for mutations in the genes for protamine 1, protamine 2 and transition protein 1. Hum Reprod 1994; 9: 2313-7
  12. de Yebra L, Ballesca JL, Vanrell JA, Corzett M, Balhom R, Oliva R. Detection of P2 precursors in the sperm cells of infertile patients who have reduced protamine P2levels. Fertil Steril 1998; 69: 755-9 https://doi.org/10.1016/S0015-0282(98)00012-0
  13. Cho C, Willis WD, Goulding EH, Jung-Ha H, Choi YC, Hecht NB, et al. Haploinsufficiency of protamine-1 or -2 causes infertility in mice. Nature Genet 2001; 28: 82-6 https://doi.org/10.1038/88313
  14. Lee HS, Choi HW, Park YS, Koong MK, Kang IS, Yoon JM, et al. Relationship between Microdeletions on the Y chromosome and defect of spermatogenesis. Kor J Fertil Steril 2002; 29: 303-10
  15. Bezold G, Lange M, Peter RU. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. N Engl J Med 2001; 344: 1172-3 https://doi.org/10.1056/NEJM200104123441517
  16. Rovio AT, Marchington DR, Donat S, Schuppe HC, Abel J, Fritsche E, et al. Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility. Nature Genet 2001; 29: 261-2 https://doi.org/10.1038/ng759
  17. Dowsing AT, Yong EL, Clark M, McLachlan RI, de Kretser DM, Trounson AO. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene. Lancet 1999; 354: 640-3 https://doi.org/10.1016/S0140-6736(98)08413-X
  18. De Meyts RE, Leffers H, Petersen JH, Andersen AG, Carlsen E, Jorgensen N, et al. CAG repeat length in androgen-receptor gene and reproductive variables in fertile and infertile men. Lancet 2002; 359: 44-6 https://doi.org/10.1016/S0140-6736(02)07280-X
  19. Fritsche E, Schuppe HC, Dohr O, Ruzicka T, Gleichmann E, Abel J. Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men. Andrologia 1998; 30: 125-8 https://doi.org/10.1111/j.1439-0272.1998.tb01387.x
  20. Oliva R, Dixon GH. Vertebrate protamine genes and the histone-to-protamine replacement reaction. Prog Nucleic Acid Res Mol Biol 1991; 40: 25-94 https://doi.org/10.1016/S0079-6603(08)60839-9
  21. Dadoune JP. The nuclear status of human sperm cells. Micron 1995; 26: 323-45 https://doi.org/10.1016/0968-4328(95)00007-0
  22. Bench G, Corzett MH, de Yebra L, Oliva R, Balhom R. Protein and DNA contents in sperm from an infertile human male possessing protamine defects that vary over time. Mol Reprod Dev 1998; 50: 345-53 https://doi.org/10.1002/(SICI)1098-2795(199807)50:3<345::AID-MRD11>3.0.CO;2-3
  23. Aoki VW, Liu L, Carrell DT. Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod 2005; 20: 1298-306 https://doi.org/10.1093/humrep/deh798
  24. Tanaka H, Miyagawa Y, Tsujimura A, Matsumiya K, Okuyama A, Nishimune Y. Single nucleotide polymorphisms in the protamine-1 and -2 genes of fertile and infertile human male populations. Mol Hum Reprod 2003; 9: 69-73 https://doi.org/10.1093/molehr/gag010