Sperm transcriptome profiling in oligozoospermia

  • Debbie Montjean
  • Pierre De La Grange
  • David Gentien
  • Audrey Rapinat
  • Stéphanie Belloc
  • Paul Cohen-Bacrie
  • Yves Menezo
  • Moncef Benkhalifa
Gamete Biology

Abstract

Purpose

Investigate in what extent sperm transcriptome of infertile men is different from that of fertile individuals.

Methods

Semen samples were collected for determination of sperm parameters as well as for RNA isolation. Gene expression profile was investigated in spermatozoa of 8 infertile and 3 fertile men by microarray analysis using the Affymetrix Chip HG-U133 Plus 2.0.

Result(s)

We observed up to 33-fold reduction expression of genes involved in spermatogenesis and sperm motility. Furthermore, there is an important decrease in expression of genes involved in DNA repair as well as oxidative stress regulation. In this study, we also show a striking drop in expression of histone modification genes.

Conclusion(s)

We found that transcription profile in germ cells of men with idiopathic infertility is different from that of fertile individuals. Interestingly, about 15% of the regulated genes (Eddy Rev Reprod 4:23–30, 1999) play a role in spermatogenesis.

Keywords

Sperm Transcripts Oligoasthenoteratozoospermia Male infertility Microarray 

References

  1. 1.
    Hauser R, Sokol R. Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult male. Fertil Steril. 2008;89:e59–65.PubMedCrossRefGoogle Scholar
  2. 2.
    O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril.;93:1–12.Google Scholar
  3. 3.
    Miller D, Briggs D, Snowden H, Hamlington J, Rollinson S, Lilford R, et al. A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis. Gene. 1999;237:385–92.PubMedCrossRefGoogle Scholar
  4. 4.
    Ostermeier GC, Dix DJ, Miller D, Khatri P, Krawetz SA. Spermatozoal RNA profiles of normal fertile men. Lancet. 2002;360:772–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Lalancette C, Platts AE, Johnson GD, Emery BR, Carrell DT, Krawetz SA. Identification of human sperm transcripts as candidate markers of male fertility. J Mol Med. 2009;87:735–48.PubMedCrossRefGoogle Scholar
  6. 6.
    Platts AE, Dix DJ, Chemes HE, Thompson KE, Goodrich R, Rockett JC, et al. Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs. Hum Mol Genet. 2007;16:763–73.PubMedCrossRefGoogle Scholar
  7. 7.
    Rousseaux S, Gaucher J, Thevenon J, Caron C, Vitte AL, Curtet S, et al. Spermiogenesis: histone acetylation triggers male genome reprogramming. Gynecol Obstet Fertil. 2009;37:519–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Altmae S, Salumets A. A novel genomic diagnostic tool for sperm quality? Reprod Biomed Online.Google Scholar
  9. 9.
    Feugang JM, Rodriguez-Osorio N, Kaya A, Wang H, Page G, Ostermeier GC, et al. Transcriptome analysis of bull spermatozoa: implications for male fertility. Reprod Biomed Online.;21:312–24.Google Scholar
  10. 10.
    Hamatani T. Spermatozoal RNA profiling towards a clinical evaluation of sperm quality. Reprod Biomed Online.;22:103–5.Google Scholar
  11. 11.
    Thomas PD, Campbell MJ, Kejariwal A, Mi H, Karlak B, Daverman R, et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 2003;13:2129–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Thomas PD, Kejariwal A, Campbell MJ, Mi H, Diemer K, Guo N, et al. PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification. Nucleic Acids Res. 2003;31:334–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Miller D, Tang PZ, Skinner C, Lilford R. Differential RNA fingerprinting as a tool in the analysis of spermatozoal gene expression. Hum Reprod. 1994;9:864–9.PubMedGoogle Scholar
  14. 14.
    Horowitz E, Zhang Z, Jones BH, Moss SB, Ho C, Wood JR, et al. Patterns of expression of sperm flagellar genes: early expression of genes encoding axonemal proteins during the spermatogenic cycle and shared features of promoters of genes encoding central apparatus proteins. Mol Hum Reprod. 2005;11:307–17.PubMedCrossRefGoogle Scholar
  15. 15.
    Liu SF, Lu GX, Liu G, Xing XW, Li LY, Wang Z. Cloning of a full-length cDNA of human testis-specific spermatogenic cell apoptosis inhibitor TSARG2 as a candidate oncogene. Biochem Biophys Res Commun. 2004;319:32–40.PubMedCrossRefGoogle Scholar
  16. 16.
    Ohinata Y, Sutou S, Kondo M, Takahashi T, Mitsui Y. Male-enhanced antigen-1 gene flanked by two overlapping genes is expressed in late spermatogenesis. Biol Reprod. 2002;67:1824–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Kempisty B, Depa-Martynow M, Lianeri M, Jedrzejczak P, Darul-Wasowicz A, Jagodzinski PP. Evaluation of protamines 1 and 2 transcript contents in spermatozoa from asthenozoospermic men. Folia Histochem Cytobiol. 2007;45 Suppl 1:S109–13.PubMedGoogle Scholar
  18. 18.
    Imken L, Rouba H, El Houate B, Louanjli N, Barakat A, Chafik A, et al. Mutations in the protamine locus: association with spermatogenic failure? Mol Hum Reprod. 2009;15:733–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Liu Z, Zhou S, Liao L, Chen X, Meistrich M, Xu J. Jmjd1a demethylase-regulated histone modification is essential for cAMP-response element modulator-regulated gene expression and spermatogenesis. J Biol Chem.;285:2758–70.Google Scholar
  20. 20.
    Alsheimer M, Liebe B, Sewell L, Stewart CL, Scherthan H, Benavente R. Disruption of spermatogenesis in mice lacking A-type lamins. J Cell Sci. 2004;117:1173–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Cao Q, Chen J, Zhu L, Liu Y, Zhou Z, Sha J, et al. A testis-specific and testis developmentally regulated tumor protein D52 (TPD52)-like protein TPD52L3/hD55 interacts with TPD52 family proteins. Biochem Biophys Res Commun. 2006;344:798–806.PubMedCrossRefGoogle Scholar
  22. 22.
    Kultgen PL, Byrd SK, Ostrowski LE, Milgram SL. Characterization of an A-kinase anchoring protein in human ciliary axonemes. Mol Biol Cell. 2002;13:4156–66.PubMedCrossRefGoogle Scholar
  23. 23.
    Christians ES, Zhou Q, Renard J, Benjamin IJ. Heat shock proteins in mammalian development. Semin Cell Dev Biol. 2003;14:283–90.PubMedCrossRefGoogle Scholar
  24. 24.
    Eddy EM. Role of heat shock protein HSP70-2 in spermatogenesis. Rev Reprod. 1999;4:23–30.PubMedCrossRefGoogle Scholar
  25. 25.
    Carrell DT. Contributions of spermatozoa to embryogenesis: assays to evaluate their genetic and epigenetic fitness. Reprod Biomed Online. 2008;16:474–84.PubMedCrossRefGoogle Scholar
  26. 26.
    Garcia-Herrero S, Garrido N, Martinez-Conejero JA, Remohi J, Pellicer A, Meseguer M. Differential transcriptomic profile in spermatozoa achieving pregnancy or not via ICSI. Reprod Biomed Online.;22:25–36.Google Scholar
  27. 27.
    Lalancette C, Miller D, Li Y, Krawetz SA. Paternal contributions: new functional insights for spermatozoal RNA. J Cell Biochem. 2008;104:1570–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Kobayashi H, Hiura H, John RM, Sato A, Otsu E, Kobayashi N, et al. DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm. Eur J Hum Genet. 2009;17:1582–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsunomiya T, et al. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet. 2007;16:2542–51.PubMedCrossRefGoogle Scholar
  30. 30.
    Marques CJ, Carvalho F, Sousa M, Barros A. Genomic imprinting in disruptive spermatogenesis. Lancet. 2004;363:1700–2.PubMedCrossRefGoogle Scholar
  31. 31.
    Marques CJ, Costa P, Vaz B, Carvalho F, Fernandes S, Barros A, et al. Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol Hum Reprod. 2008;14:67–74.PubMedCrossRefGoogle Scholar
  32. 32.
    Poplinski A, Tuttelmann F, Kanber D, Horsthemke B, Gromoll J. Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2/H19 ICR1. Int J Androl.;33:642–9.Google Scholar
  33. 33.
    Ostermeier GC, Miller D, Huntriss JD, Diamond MP, Krawetz SA. Reproductive biology: delivering spermatozoan RNA to the oocyte. Nature. 2004;429:154.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Debbie Montjean
    • 1
    • 2
  • Pierre De La Grange
    • 3
  • David Gentien
    • 4
  • Audrey Rapinat
    • 4
  • Stéphanie Belloc
    • 2
  • Paul Cohen-Bacrie
    • 2
  • Yves Menezo
    • 2
  • Moncef Benkhalifa
    • 1
    • 2
  1. 1.Advanced Technology LaboratoryParisFrance
  2. 2.Laboratoire d’Eylau, UnilabsParisFrance
  3. 3.GenoSplice TechnologyParisFrance
  4. 4.Platform of Molecular Biology Facilities, Translational Research Department, Research centerInstitut CurieParisFrance

Personalised recommendations