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Scientific article
Open access
English

The molecular chaperone Hsp90alpha is required for meiotic progression of spermatocytes beyond pachytene in the mouse

Published inPloS one, vol. 5, no. 12, e15770
Publication date2010
Abstract

The molecular chaperone Hsp90 has been found to be essential for viability in all tested eukaryotes, from the budding yeast to Drosophila. In mammals, two genes encode the two highly similar and functionally largely redundant isoforms Hsp90alpha and Hsp90beta. Although they are co-expressed in most if not all cells, their relative levels vary between tissues and during development. Since mouse embryos lacking Hsp90beta die at implantation, and despite the fact that Hsp90 inhibitors being tested as anti-cancer agents are relatively well tolerated, the organismic functions of Hsp90 in mammals remain largely unknown. We have generated mouse lines carrying gene trap insertions in the Hsp90alpha gene to investigate the global functions of this isoform. Surprisingly, mice without Hsp90alpha are apparently normal, with one major exception. Mutant male mice, whose Hsp90beta levels are unchanged, are sterile because of a complete failure to produce sperm. While the development of the male reproductive system appears to be normal, spermatogenesis arrests specifically at the pachytene stage of meiosis I. Over time, the number of spermatocytes and the levels of the meiotic regulators and Hsp90 interactors Hsp70-2, NASP and Cdc2 are reduced. We speculate that Hsp90alpha may be required to maintain and to activate these regulators and/or to disassemble the synaptonemal complex that holds homologous chromosomes together. The link between fertility and Hsp90 is further supported by our finding that an Hsp90 inhibitor that can cross the blood-testis barrier can partially phenocopy the genetic defects.

Keywords
  • Animals
  • Blood-Testis Barrier
  • Disease Progression
  • Female
  • HSP90 Heat-Shock Proteins/*metabolism
  • Male
  • Meiosis
  • Mice
  • Molecular Chaperones/*metabolism
  • Mutation
  • *Pachytene Stage
  • Phenotype
  • Spermatocytes/*cytology
  • Spermatogenesis
  • Spermatozoa/physiology
  • Testis/*metabolism
Citation (ISO format)
GRAD, Iwona et al. The molecular chaperone Hsp90alpha is required for meiotic progression of spermatocytes beyond pachytene in the mouse. In: PloS one, 2010, vol. 5, n° 12, p. e15770. doi: 10.1371/journal.pone.0015770
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Article (Published version)
Identifiers
ISSN of the journal1932-6203
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343downloads

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