title: Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice.
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.
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Abo Akademi University, FIN-20520 Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Kallio
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Chang
authors.forename: Martine
authors.initials: M
authors.lastname: Manuel
authors.forename: Tero-Pekka
authors.initials: TP
authors.lastname: Alastalo
authors.forename: Murielle
authors.initials: M
authors.lastname: Rallu
authors.forename: Yorick
authors.initials: Y
authors.lastname: Gitton
authors.forename: Lila
authors.initials: L
authors.lastname: Pirkkala
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Loones
authors.forename: Liliana
authors.initials: L
authors.lastname: Paslaru
authors.forename: Severine
authors.initials: S
authors.lastname: Larney
authors.forename: Sophie
authors.initials: S
authors.lastname: Hiard
authors.forename: Michel
authors.initials: M
authors.lastname: Morange
authors.forename: Lea
authors.initials: L
authors.lastname: Sistonen
authors.forename: Valérie
authors.initials: V
authors.lastname: Mezger
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism*; D002875:Chromosomes / Q000648:ultrastructure*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics; D005822:Genetic Vectors; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006579:Heterozygote; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000235:genetics*; D007763:Lac Operon; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D010053:Ovary / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013737:Testis / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human; D001616:beta-Galactosidase