Human Genetics

, Volume 113, Issue 6, pp 486–492

Members of the CDY family have different expression patterns: CDY1 transcripts have the best correlation with complete spermatogenesis

  • Sandra E. Kleiman
  • Leah Yogev
  • Ron Hauser
  • Amnon Botchan
  • Batia Bar-Shira Maymon
  • Letizia Schreiber
  • Gedalia Paz
  • Haim Yavetz
Original Investigation

Abstract

The CDY family of genes is of special interest because some of them are included in chromosome-Y microdeletions detected among infertile men and are apparently involved in the spermiogenetic process. In this study, we employed the reverse transcriptase/polymerase chain reaction technique to test the RNA expression of the various transcripts of these genes in testicular biopsies of 84 azoospermic men who had been classified by comprehensive histology and cytology analyses. We also evaluated the feasibility of detecting CDY expression in biopsies taken by testicular sperm extraction versus acquisition by aspiration. There was a significant association between the type of testicular impairment and the expression of CDY1 and CDY2 transcripts. CDY2 was expressed whenever germ cells were present, but CDY1 major and especially CDY1 minor and short transcripts were identified almost exclusively when mature spermatids/spermatozoa were detected. The expression of CDY1 minor and short transcripts detected in aspirated specimens was less efficient than that in testicular tissue acquired by extraction. It is sugested that CDY2 is apparently required in the early stages of spermatogenesis, whereas CDY1 transcripts are required later on in the process. The findings of this study imply different functional roles for CDY isoforms during spermatogenesis. However, in consideration of the high levels of identity between CDY1 and CDY2 (98% at the protein level), the delayed up-regulation of CDY1 transcripts could be attributable to temporal changes in dosage requirements.

References

  1. Bar-Shira Maymon B, Elliott DJ, Kleiman SE, Yogev L, Hauser R, Botchan A, Schreiber L, Cooke HJ, Paz G, Yavetz H (2001) The contribution of RNA-binding motif (RBM) antibody to the histopathologic evaluation of testicular biopsies from infertile men. Hum Pathol 32:36–41CrossRefPubMedGoogle Scholar
  2. Ben-Yosef D, Yogev L, Hauser R, Hauser R, Yavetz H, Azem F, Yovel I, Lessing JB, Amit A (1999) Testicular sperm retrieval and cryopreservation prior to initiating ovarian stimulation as the first line approach in men with non-obstructive azoospermia. Hum Reprod 14:1794–1801CrossRefPubMedGoogle Scholar
  3. Eddy EM (1998) Regulation of gene expression during spermatogenesis. Semin Cell Dev Biol 9:451–457CrossRefPubMedGoogle Scholar
  4. Edwards RG, Bishop CE (1997) On the origin and frequency of the Y chromosome deletions responsible for severe male infertility. Mol Hum Reprod 3:549–554PubMedGoogle Scholar
  5. Elliott DJ, Oghene K, Makarov G, Makarova O, Hargreave TB, Chandley AC, Eperon IC, Cooke HJ (1998) Dynamic changes in the subnuclear organization of pre-mRNA splicing proteins and RBM during human germ cell development. J Cell Science 111:1255–1265PubMedGoogle Scholar
  6. Elliott DJ, Bourgeois CF, Klink A, Stevenin J, Cooke HJ (2000) A mammalian germ cell-specific RNA-binding protein interacts with ubiquitously expressed proteins involved in splice site selection. Proc Natl Acad Sci USA 97:5717–5722CrossRefPubMedGoogle Scholar
  7. Ezeh UI, Moore HD, Cooke ID (1998) A prospective study of multiple needle biopsies versus a single open biopsy for testicular sperm extraction in men with non-obstructive azoospermia. Hum Reprod 13:3075–3080CrossRefPubMedGoogle Scholar
  8. Friedler S, Raziel A, Strassburger D, Soffer Y, Komarovsky D, Ron-El R (1997) Testicular sperm retrieval by percutaneous fine needle sperm aspiration compared with testicular sperm extraction by open biopsy in men with non-obstructive azoospermia. Hum Reprod 12:1488–1493CrossRefPubMedGoogle Scholar
  9. Hauser R, Botchan A, Amit A, Ben Yosef D, Gamzu R, Paz G, Lessing JB, Yogev L, Yavetz H (1998) Multiple testicular sampling in non-obstructive azoospermia—is it necessary? Hum Reprod 13:3081–3085CrossRefPubMedGoogle Scholar
  10. Hazzouri M, Pivot-Pajot C, Faure AK, Usson Y, Pelletier R, Sele B, Khochbin S, Rousseaux S (2000) Regulated hyperacetylation of core histones during mouse spermatogenesis: involvement of histone deacetylases. Eur J Cell Biol 79:950–960PubMedGoogle Scholar
  11. Kleene KC (2001) A possible meiotic function of the peculiar patterns of gene expression in mammalian spermatogenic cells. Mech Dev 106:3–23CrossRefPubMedGoogle Scholar
  12. Kleiman SE, Yogev L, Gamzu R, Hauser R, Botchan A, Lessing JB, Paz G, Yavetz H (1999) Genetic evaluation of infertile men. Hum Reprod 14:33–38CrossRefPubMedGoogle Scholar
  13. Kleiman SE, Lagziel A, Yogev L, Botchan A, Paz G, Yavetz H (2001) Expression of CDY1 may identify complete spermatogenesis. Fertil Steril 75:166–173CrossRefPubMedGoogle Scholar
  14. Kobayashi, K, Mizuno K, Hida A, Komaki R, Tomita K, Matsushita I, Namiki M, Iwamoto T, Tamura S, Minowada S (1994) PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis. Hum Mol Genet 3:1965–1967PubMedGoogle Scholar
  15. Kostova E, Rottger S, Schempp W, Gromoll J (2002) Identification and characterization of the cynomolgus monkey chromodomain gene cynCDY, an orthologue of the human CDY gene family. Mol Hum Reprod 8:702–709CrossRefPubMedGoogle Scholar
  16. Kuroda-Kawaguchi T, Skaletsky H, Brown LG, Minx PJ, Cordum HS, Waterston RH, Wilson RK, Silber S, Oates R, Rozen S, Page DC (2001) The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet 29:279–286CrossRefPubMedGoogle Scholar
  17. Lahn BT, Page DC (1997) Functional coherence of the human Y chromosome. Science 278:675–680CrossRefPubMedGoogle Scholar
  18. Lahn BT, Page DC (1999) Retroposition of autosomal mRNA yielded testis-specific gene family on human Y chromosome. Nat Genet 21:429–433CrossRefPubMedGoogle Scholar
  19. Lahn BT, Tang ZL, Zhou J, Barndt RJ, Parvinen M, Allis CD, Page DC (2002) Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis. Proc Natl Acad Sci USA 99:8707–8712CrossRefPubMedGoogle Scholar
  20. Lee JH, Lee DR, Yoon SJ, Chai YG, Roh SI, Yoon HS (1998) Expression of DAZ (deleted in azoospermia), DAZL1 (DAZ-like) and protamine-2 in testis and its application for diagnosis of spermatogenesis in non-obstructive azoospermia. Mol Hum Reprod 4:827–834CrossRefPubMedGoogle Scholar
  21. Lewin A, Reubinoff B, Porat-Katz A, Weiss D, Eisenberg V, Arbel R, Bar-el H, Safran A (1999) Testicular fine needle aspiration: the alternative method for sperm retrieval in non-obstructive azoospermia Hum Reprod 14:1785–1790Google Scholar
  22. Ma K, Inglis JD, Sharkey A, Bickmore WA, Hill RE, Prosser EJ, Speed RM, Thomson EJ, Jobling M, Taylor K (1993) A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 75:1287–1295PubMedGoogle Scholar
  23. Menke DB, Mutter GL, Page DC (1997) Expression of DAZ, an azoospermia factor candidate, in human spermatogonia. Am J Hum Genet 60:237–241PubMedGoogle Scholar
  24. Meistrich ML, Trostle-Weiga PK, Lin R, Bhatnagar YM, Allis CD (1992) Highly acetylated H4 is associated with histone displacement in rat spermatids. Mol Reprod Dev 31:170–181PubMedGoogle Scholar
  25. Oates RD, Silber S, Brown LG, Page DC. (2002) Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod 17:2813–2824CrossRefPubMedGoogle Scholar
  26. Pryor JL, Kent-First M, Muallem A, Van Bergen AH, Nolten WE, Meisner L, Roberts KP (1997) Microdeletions in the Y chromosome of infertile men. N Engl J Med 336:534–539CrossRefPubMedGoogle Scholar
  27. Reijo R, Lee TY, Alagappan R, Brown LG, Rosenberg M, Rozen S, Jaffe T, Straus D, Hovatta O, Chapelle A de la, Silver S, Page DC (1995) Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 10:383–392PubMedGoogle Scholar
  28. Repping S, Skaletsky H, Lange J, Silber S, Van Der Veen F, Oates RD, Page DC, Rozen S (2002) Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet 71:906–922CrossRefPubMedGoogle Scholar
  29. Schrader M, Muller M, Schulze W, Heicappell R, Krause H, Straub B, Miller K (2002a) Quantification of the expression level of the gene encoding the catalytic subunit of telomerase in testicular tissue specimens predicts successful sperm recovery. Hum Reprod 17:150–156CrossRefPubMedGoogle Scholar
  30. Schrader M, Muller-Tidow C, Ravnik S, Muller M, Schulze W, Diederichs S, Serve H, Miller K (2002b) Cyclin A1 and gametogenesis in fertile and infertile patients: a potential new molecular diagnostic marker. Hum Reprod 17:2338–2343CrossRefPubMedGoogle Scholar
  31. Silber SJ, Nagy S, Devroey P, Tournaye H, Van Steirteghem AC (1997) Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure. Hum Reprod 12:2422–2428PubMedGoogle Scholar
  32. Tiepolo L, Zuffardi O (1976) Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 34:119–124PubMedGoogle Scholar
  33. Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Kohn FM, Schill WB, Farah S, Ramos C, Hartmann M, Hartschuh W, Meschede D, Behre HM, Castel A, Nieschlag E, Weidner W, Grone HJ, Jung A, Engel W, Haidl G (1996) Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet 5:933–943PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Sandra E. Kleiman
    • 1
  • Leah Yogev
    • 1
  • Ron Hauser
    • 1
  • Amnon Botchan
    • 1
  • Batia Bar-Shira Maymon
    • 2
  • Letizia Schreiber
    • 2
  • Gedalia Paz
    • 1
  • Haim Yavetz
    • 1
  1. 1.Institute for the Study of Fertility, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  2. 2.Institute of Pathology, Tel Aviv Sourasky Medical Center, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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