Skip to main content
Log in

Molecular biological features of male germ cell differentiation

  • Review Article
  • Gametogenesis
  • Published:
Reproductive Medicine and Biology

Abstract

Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Tanaka H, Baba T. Gene expression in spermiogenesis.Cell Mol Life Sci 2005;62: 344–354.

    Article  PubMed  CAS  Google Scholar 

  2. Skakkebaek NE, Jorgensen N, Main KMet al. Is human fecundity declining?Int J Androl 2006;29: 2–11.

    Article  PubMed  Google Scholar 

  3. McLaren A. Primordial germ cells in the mouse.Dev Biol 2003;262: 1–15.

    Article  PubMed  CAS  Google Scholar 

  4. McLaren A, Southee D. Entry of mouse embryonic germ cells into meiosis.Dev Biol 1997;187: 107–113.

    Article  PubMed  CAS  Google Scholar 

  5. Adams IR, McLaren A. Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis.Development 2002;129: 1155–1164.

    PubMed  CAS  Google Scholar 

  6. Amleh A, Taketo T. Live-boms from XX but not XY oocytes in the chimeric mouse ovary composed of B6.Y (TIR) and XX cells.Biol Reprod 1998;58: 574–582.

    Article  PubMed  CAS  Google Scholar 

  7. Isotani A, Nakanishi T, Kobayashi Set al. Genomic imprinting of XX spermatogonia and XX oocytes recovered from XX↔XY chimeric testes.Proc Natl Acad Sci USA 2005;102: 4039–4044.

    Article  PubMed  CAS  Google Scholar 

  8. Tanaka SS, Toyooka Y, Akasu Ret al. The mouse homolog ofDrosophila vasa is required for the development of male germ cells.Genes Dev 2000;4: 841–853.

    Google Scholar 

  9. Kuramochi-Miyagawa S, Kimura T, Ijiri TWet al.Mili, a mammalian member ofpiwi family gene, is essential for spermatogenesis.Development 2004;131: 839–849.

    Article  PubMed  CAS  Google Scholar 

  10. Guan K, Nayernia K, Maier LSet al. Pluripotency of spermatogonial stem cells from adult mouse testis.Nature 2006;440: 1199–1203.

    Article  PubMed  CAS  Google Scholar 

  11. Heller CG, Clermont Y. Spermatogenesis in man: an estimate of its duration.Science 1963;140: 184–186.

    Article  PubMed  CAS  Google Scholar 

  12. Penttila TL, Yuan L, Mali Pet al. Haploid gene expression: temporal onset and storage patterns of 13 novel transcripts during rat and mouse spermiogenesis.Biol Reprod 1995;53: 499–510.

    Article  PubMed  CAS  Google Scholar 

  13. de Rooij DG. Stem cells in the testis.Int J Exp Pathol 1998;79: 67–80.

    Article  PubMed  Google Scholar 

  14. Matzuk MM, Lamb DJ. Genetic dissection of mammalian fertility pathways.Nat Cell Biol 2002;4: S41-S49.

    Article  PubMed  Google Scholar 

  15. Fujii T, Tamura K, Masai Ket al. Use of stepwise subtraction to comprehensively isolate mouse genes whose transcription is up-regulated during spermiogenesis.EMBO Rep 2002;3: 367–372.

    Article  PubMed  CAS  Google Scholar 

  16. Nishimune Y, Tanaka H. Infertility caused by polymorphisms or mutations in spermatogenesis-specific genes.J Androl 2006;27: 326–334.

    Article  PubMed  CAS  Google Scholar 

  17. Nantel F, Monaco L, Foulkes NSet al. Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice.Nature 1996;380: 159–162.

    Article  PubMed  CAS  Google Scholar 

  18. Fimia GM, De Cesare D, Sassone-Corsi P. CBP-independent activation of CREM and CREB by the LIM-only protein ACT.Nature 1999;398: 165–169.

    Article  PubMed  CAS  Google Scholar 

  19. Nagamori I, Yomogida K, Adams PDet al. Transcription factors, cAMP-responsive element modulator (CREM) and Tisp40, act in concert in postmeiotic transcriptional regulation.J Biol Chem 2006;281: 15073–15081.

    Article  PubMed  CAS  Google Scholar 

  20. Macho B, Brancorsini S, Fimia GMet al. CREM-dependent transcription in male germ cells controlled by a kinesin.Science 2002;298: 2388–2390.

    Article  PubMed  CAS  Google Scholar 

  21. Schmidt EE, Schibler U. Developmental testis-specific regulation of mRNA levels and mRNA translational efficiencies for TATA-binding protein mRNA isoforms.Dev Biol 1997;184: 138–149.

    Article  PubMed  CAS  Google Scholar 

  22. Walker WH, Delfino FJ, Habener JF. RNA processing and the control of spermatogenesis.Front Harm Res 1999;25: 34–58.

    Article  CAS  Google Scholar 

  23. Blocher S, Behr R, Weinbauer GF, Bergmann M, Steger K. Different CREM-isoform gene expression between equine and human normal and impaired spermatogenesis.Theriogenology 2003;60: 1357–1369.

    Article  PubMed  CAS  Google Scholar 

  24. Walker WH, Daniel PB, Habener JF. Inducible cAMP early represser ICER down-regulation of CREB gene expression in Sertoli cells.Mol Cell Endocrinol 1998;143: 167–178.

    Article  PubMed  CAS  Google Scholar 

  25. Morales CR, Leyne M, El-Alfy M, Oko R. Molecular cloning and developmental expression of a small ribonuclear protein in the mouse testis.Mol Reprod Dev 1997;46: 459–470.

    Article  PubMed  CAS  Google Scholar 

  26. Elliott DJ, Bourgeois CF, Klink Aet al. A mammalian germ cell-specific RNA-binding protein interacts with ubiquitously expressed proteins involved in splice site selection.Proc Natl Acad Sci USA 2000;97: 5717–5722.

    Article  PubMed  CAS  Google Scholar 

  27. Ostermeier GC, Dix DJ, Miller Det al. Spermatozoal RNA profiles of normal fertile men.Lancet 2002;360: 772–777.

    Article  PubMed  CAS  Google Scholar 

  28. Rassoulzadegan M, Grandjean V, Gounon Pet al. RNA-mediated non-Mendelian inheritance of an epigenetic change in the mouse.Nature 2006;441: 469–474.

    Article  PubMed  CAS  Google Scholar 

  29. Morales CR, Wu XQ, Hecht NB. The DNA/RNA-binding protein, TB-RBP, moves from the nucleus to the cytoplasm and through intercellular bridges in male germ cells.Dev Biol 1998;201: 113–123.

    Article  PubMed  CAS  Google Scholar 

  30. Iguchi N, Tobias JW, Hecht NB. Expression profiling reveals meiotic male germ cell mRNAs that are translationally up and down-regulated.Proc Natl Acad Sci USA 2006; 103: 7712–7717.

    Article  PubMed  CAS  Google Scholar 

  31. Kashiwabara S, Noguchi J, Zhuang Tet al. Regulation of spermatogenesis by testis-specific, cytoplasmic poly (A) polymerase TPAP.Science 2002; 298: 1999–2002.

    Article  PubMed  CAS  Google Scholar 

  32. Han JR, Yiu GK, Hecht NB. Testis/brain RNA-binding protein attaches translationally repressed and transported mRNAs to microtubules.Proc Natl Acad Sci USA 1995;92: 9550–9554.

    Article  PubMed  CAS  Google Scholar 

  33. Mali P, Kaipia A, Kangasniemi Met al. Stage-specific expression of nucleoprotein mRNAs during rat and mouse spermiogenesis.Reprod Fertil Dev 1989;1: 369–382.

    Article  PubMed  CAS  Google Scholar 

  34. Chennathukuzhi V, Stein JM, Abel Tet al. Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes.Mol Cell Biol 2003;23: 6419–6434.

    Article  PubMed  CAS  Google Scholar 

  35. Chennathukuzhi V, Morales CR, El-Alfy M, Hecht NB. The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells.Proc Natl Acad Sci USA 2003;100: 15566–15571.

    Article  PubMed  CAS  Google Scholar 

  36. Morales CR, Lefrancois S, Chennathukuzhi Vet al. A TB-RBP and Ter ATPase complex accompanies specific mRNAs from nuclei through the nuclear pores and into intercellular bridges in mouse male germ cells.Dev Biol 2002;246: 480–494.

    Article  PubMed  CAS  Google Scholar 

  37. Lee K, Fajardo MA, Braun RE. A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor.Mol Cell Biol 1996;16: 3023–3034.

    PubMed  CAS  Google Scholar 

  38. Davies HG, Giorgini F, Fajardo MA, Braun RE. A sequencespecific RNA binding complex expressed in murine germ cells contains MSY2 and MSY4.Dev Biol 2000;221: 87–100.

    Article  PubMed  CAS  Google Scholar 

  39. Schumacher JM, Lee K, Edelhoff S, Braun RE. Spnr, a murine RNA-binding protein that is localized to cytoplasmic microtubules.J Cell Biol 1995;129: 1023–1032.

    Article  PubMed  CAS  Google Scholar 

  40. Kleene KC, Mulligan E, Steiger Det al. The mouse gene encoding the testis-specific isoform of Poly (A) binding protein (Pabp2) is an expressed retroposon: intimations that gene expression in spermatogenic cells facilitates the creation of new genes.J Mol Evol 1998;47: 275–281.

    Article  PubMed  CAS  Google Scholar 

  41. Gu W, Kwon Y, Oko Ret al. Poly (A) binding protein is bound to both stored and polysomal mRNAs in the mammalian testis.Mol Reprod Dev 1995;40: 273–285.

    Article  PubMed  CAS  Google Scholar 

  42. Skaletsky H, Kuroda-Kawaguchi Tet al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes.Nature 2003;423: 825–837.

    Article  PubMed  CAS  Google Scholar 

  43. Koopman P, Munsterberg A, Capel Bet al. Expression of a candidate sex-determining gene during mouse testis differentiation.Nature 1990;348: 450–452.

    Article  PubMed  CAS  Google Scholar 

  44. Vogt PH. AZF deletions and Y chromosomal haplogroups: history and update based on sequence.Hum Reprod Update 2005;11: 319–336.

    Article  PubMed  CAS  Google Scholar 

  45. Hopps CV, Mielnik A, Goldstein Met al. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions.Hum Reprod 2003;18: 1660–1665.

    Article  PubMed  CAS  Google Scholar 

  46. Silber SJ, Repping S. Transmission of male infertility to future generations: lessons from the Y chromosome.Hum Reprod Update 2002;8: 217–229.

    Article  PubMed  Google Scholar 

  47. Miki K, Qu W, Goulding EHet al. Glyceraldehyde-3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility.Proc Natl Acad Sci USA 2004;101: 16501–16506.

    Article  PubMed  CAS  Google Scholar 

  48. Piechaczyk M, Blanchard JM, Marty Let al. Post-transcriptional regulation of glyceraldehyde-3-phosphatedehydrogenase gene expression in rat tissues.Nucl Acids Res 1984;12: 6951–6963.

    Article  PubMed  CAS  Google Scholar 

  49. Hecht NB. Molecular mechanisms of male germ cell differentiation.Bioessays 1998;20: 555–561.

    Article  PubMed  CAS  Google Scholar 

  50. Tanaka H, Miyagawa Y, Tsujimura Aet al. Single nudeotide polymorphisms in the protamine-1 and 2 genes of fertile and infertile human male populations.Mol Hum Reprod 2003;9: 69–73.

    Article  PubMed  CAS  Google Scholar 

  51. Becherini L, Guarducd E. Degl’Innocenti Set al. DAZL poly-morphisms and susceptibility to spermatogenic failure: an example of remarkable ethnic differences,Int J Androl 2004;27: 375–381.

    Article  PubMed  CAS  Google Scholar 

  52. Miyagawa Y, Nishimura H, Tsujimura Aet al. Singlenucleotide polymorphisms and mutation analyses of theTNP1 andTNP2 genes of fertile and infertile human male populations.J Androl 2005;26: 779–786.

    Article  PubMed  CAS  Google Scholar 

  53. Singh K, Singh SK, Sah Ret al. Mutation C677T in the methylenetetrahydrofolate reductase gene is associated with male infertility in an Indian population.Int J Androl 2005;28: 115–119.

    Article  PubMed  CAS  Google Scholar 

  54. Longley MJ, Graziewicz MA, Bienstock RJ, Copeland WC. Consequences of mutations in human DNA polymerase gamma.Gene 2005;354: 125–131.

    Article  PubMed  CAS  Google Scholar 

  55. Zhoucun A, Zhang S, Yang Yet al. The common variant N372H inBRCA2 gene may be associated with idiopathic male infertility with azoospermia or severe oligozoospermia.Eur J Obstet Gynecol Reprod Biol 2006;124: 61–64.

    Article  PubMed  CAS  Google Scholar 

  56. Iguchi N, Yang S, Lamb DJ, Hecht NB. An SNP in protamine 1: a possible genetic cause of male infertility?J Med Genet 2006;43: 382–384.

    Article  PubMed  CAS  Google Scholar 

  57. A Z, Zhang S, Yang Yet al. Single nucleotide polymorphisms of the gonadotrophin-regulated testicular helicase (GRTH) gene may be associated with the human spermatogenesis impairment.Hum Reprod 2006;21: 755–759.

    PubMed  Google Scholar 

  58. Christensen GL, Wooding SP, Ivanov IPet al. Sequencing and haplotype analysis of the Activator of CREM in the Testis (ACT) gene in populations of fertile and infertile males.Mol Hum Reprod 2006;12: 257–262.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiromitsu Tanaka.

About this article

Cite this article

Tanaka, H., Hirose, M., Tokuhiro, K. et al. Molecular biological features of male germ cell differentiation. Reprod Med Biol 6, 1–9 (2007). https://doi.org/10.1111/j.1447-0578.2007.00158.x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1111/j.1447-0578.2007.00158.x

Key words

Navigation