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Mutation of Eif4g3, encoding a eukaryotic translation initiation factor, causes male infertility and meiotic arrest

Fengyun Sun1, Kristina Palmer, Mary Ann Handel

  • 1The Jackson Laboratory, Bar Harbor, ME 04609, USA.

Development (Cambridge, England)
|May 1, 2010
PubMed

Insights

The repro8 mutation in Eif4g3 causes male infertility by blocking meiotic exit. This study shows EIF4G3 is essential for HSPA2 translation, controlling spermatocyte progression.

Area of Science:

  • Reproductive biology
  • Molecular genetics
  • Cell biology

Background:

  • Gametogenesis requires precise gene regulation for successful meiosis.
  • Male infertility can arise from defects in meiotic progression.
  • Selective translational control plays a role in cellular differentiation.

Purpose of the Study:

  • To identify genes controlling mouse gametogenesis.
  • To elucidate the molecular mechanism underlying the repro8 mutation's male-infertility phenotype.
  • To investigate the role of eukaryotic translation initiation factor 4, gamma 3 (EIF4G3) in spermatogenesis.

Main Methods:

  • ENU mutagenesis screen in mice.
  • Analysis of meiotic progression in mutant spermatocytes.
  • Assessment of protein levels and kinase activity.
  • Gene expression analysis (transcript presence vs. protein absence).

Main Results:

  • The repro8 mutation in Eif4g3 causes male-limited infertility due to failed meiotic exit (G2/MI transition).
  • Mutant spermatocytes show reduced CDC2A (CDK1) kinase activity and absent HSPA2 protein, despite normal Hspa2 transcript levels.
  • EIF4G3 is crucial for the translation of HSPA2, a chaperone for CDC2A kinase.

Conclusions:

  • EIF4G3 is essential for HSPA2 translation in mouse spermatocytes.
  • This study provides the first genetic evidence for selective translational control of meiotic exit in mammalian spermatocytes.
  • Defective translational control of HSPA2 by EIF4G3 leads to male infertility.

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