Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice

Marko Kallio, Yunhua Chang, Martine Manuel, Tero-Pekka Alastalo, Murielle Rallu, Yorick Gitton, Lila Pirkkala, Marie-Thérèse Loones, Liliana Paslaru, Severine Larney, Sophie Hiard, Michel Morange, Lea Sistonen, Valérie Mezger

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Heat shock factor 2, one of the four vertebrate HSFs, transcriptional regulators of heat shock gene expression, is active during embryogenesis and spermatogenesis, with unknown functions and targets. By disrupting the Hsf2 gene, we show that, although the lack of HSF2 is not embryonic lethal, Hsf2(-/-) mice suffer from brain abnormalities, and meiotic and gameto genesis defects in both genders. The disturbances in brain are characterized by the enlargement of lateral and third ventricles and the reduction of hippocampus and striatum, in correlation with HSF2 expression in proliferative cells of the neuroepithelium and in some ependymal cells in adults. Many developing spermatocytes are eliminated via apoptosis in a stage-specific manner in Hsf2(-/-) males, and pachytene spermatocytes also display structural defects in the synaptonemal complexes between homologous chromosomes. Hsf2(-/-) females suffer from multiple fertility defects: the production of abnormal eggs, the reduction in ovarian follicle number and the presence of hemorrhagic cystic follicles are consistent with meiotic defects. Hsf2(-/-) females also display hormone response defects, that can be rescued by superovulation treatment, and exhibit abnormal rates of luteinizing hormone receptor mRNAs.

Original languageEnglish
Pages (from-to)2591-601
Number of pages11
JournalEMBO Journal
Volume21
Issue number11
DOIs
Publication statusPublished - 3 Jun 2002
MoE publication typeA1 Journal article-refereed

Keywords

  • Alleles
  • Animals
  • Apoptosis
  • Blotting, Western
  • Brain/abnormalities
  • Chromosomes/ultrastructure
  • Embryo, Mammalian/metabolism
  • Female
  • Fertility/genetics
  • Genetic Vectors
  • Genotype
  • Heat-Shock Proteins/genetics
  • Heterozygote
  • Immunohistochemistry
  • Infertility, Female/genetics
  • Lac Operon
  • Male
  • Meiosis
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Models, Genetic
  • Ovary/metabolism
  • Promoter Regions, Genetic
  • Recombination, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors
  • Testis/metabolism
  • Time Factors
  • Transcription Factors/genetics
  • beta-Galactosidase/metabolism

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