PL EN


Preferences help
enabled [disable] Abstract
Number of results
2003 | 50 | 2 | 535-541
Article title

Expression of a constitutively active mutant of heat shock factor 1 under the control of testis-specific hst70 gene promoter in transgenic mice induces degeneration of seminiferous epithelium.

Content
Title variants
Languages of publication
EN
Abstracts
EN
Heat shock activates in somatic cells a set of genes encoding heat shock proteins which function as molecular chaperones. The basic mechanism by which these genes are activated is the interaction of the specific transcription factor HSF1 with a regulatory DNA sequence called heat shock element (HSE). In higher eukaryotes HSF1 is present in unstressed cells as inactive monomers which, in response to cellular stress, aggregate into transcriptionally competent homotrimers. In the present paper we showed that the expression of a transgene encoding mutated constitutively active HSF1 placed under the control of a spermatocyte-specific promoter derived from the hst70 gene severely affects spermatogenesis. We found the testes of transgenic mice to be significantly smaller than those of wild-type males and histological analysis showed massive degeneration of the seminiferous epithelium. The lumen of tubules was devoid of spermatids and spermatozoa and using the TUNEL method we demonstrated a high rate of spermatocyte apoptosis. The molecular mechanism by which constitutively active HSF1 arrests spermatogenesis is not known so far. One can assume that HSF1 can either induce or repress so far unknown target genes involved in germ cell apoptosis.
Year
Volume
50
Issue
2
Pages
535-541
Physical description
Dates
published
2003
received
2002-11-19
revised
2003-02-11
accepted
2003-05-21
References
  • Chomczynski P, Sacchi N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem.; 162: 156-9.
  • Chowdhury AK, Steinberger E. (1970) Early changes in the germinal epithelium of rat testes following exposure to heat. J Reprod Fertil.; 22: 205-12.
  • Dix DJ. (1997) Hsp70 expression and function during gametogenesis. Cell Stress Chaperones.; 2: 73-7.
  • Gething MJ, Sambrook J. (1992) Protein folding in the cell. Nature.; 355: 33-45.
  • Jannes P, Spiessens C, Van der Auwera I, D'Hooghe T, Verhoeven G, Vanderschueren D. (1998) Male subfertility induced by acute scrotal heating affects embryo quality in normal female mice. Hum Reprod.; 13: 372-5.
  • Krawczyk Z, Wisniewski J, Biesiada E. (1987) A hsp70-related gene is constitutively highly expressed in testis of rat and mouse. Mol Biol Rep.; 12: 27-34.
  • Lue YH, Hikim AP, Swerdloff RS, Im P, Taing KS, Bui T, Leung A, Wang C. (1999) Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology.; 140: 1709-17.
  • Matsui Y. (1998) Regulation of germ cell death in mammalian gonads. APMIS.; 106: 142-8.
  • Matsumoto M, Fujimoto H. (1990) Cloning of a hsp70-related gene expressed in mouse spermatids. Biochem Biophys Res Commun.; 166: 43-9.
  • Nakai A, Suzuki M, Tanabe M. (2000) Arrest of spermatogenesis in mice expressing an active heat shock transcription factor 1. EMBO J.; 19: 1545-54.
  • Parvinen M. (1982) Regulation of the seminiferous epithelium. Endocr Rev.; 3: 404-17.
  • Satyal SH, Morimoto RI. (1998) Biochemical events in the activation of the heat shock transcriptional response. J Biosci.; 23: 303-11.
  • Singer-Sam J, Robinson MO, Bellve AR, Simon MI, Riggs AD. (1990) Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spermatogenesis. Nucleic Acids Res.; 18: 1255-9.
  • Scieglinska D, Widlak W, Rusin M, Markkula M, Krawczyk Z. (1997) Expression of the testis-specific HSP70-related gene (hst70 gene) in somatic non-testicular rat tissues revealed by RT-PCR and transgenic mice analysis. Cell Biol Int.; 21: 813-21.
  • Scieglinska D, Widlak W, Konopka W, Poutanen M, Rahman N, Huhtaniemi I, Krawczyk Z. (2001) Structure of the 5' region of the hst70 gene transcription unit: presence of an intron and multiple transcription sites. Biochem J.; 359: 129-37.
  • Walter L, Rauch F, Gunther E. (1994) Comparative analysis of the three major histocompatibility complex-linked heat shock protein 70 (Hsp70) genes of the rat. Immunogenetics.; 40: 325-30.
  • Widlak W, Markkula M, Krawczyk Z, Huhtaniemi I. (1994) Functional analysis of spermatocyte- specific hst70 gene promoter in transgenic mice. Acta Biochim Polon.; 41: 103-5.
  • Widlak W, Markkula M, Krawczyk Z, Kananen K, Huhtaniemi I. (1995) A 252 bp upstream region of the rat spermatocyte-specific hst70 gene is sufficient to promote expression of the hst70-CAT hybrid gene in testis and brain of transgenic mice. Biochim Biophys Acta.; 1264: 191-200.
  • Wisniewski J, Kordula T, Krawczyk Z. (1990). Isolation and nucleotide sequence analysis of rat testis-specific major heat shock (hsp70)-related gene. Biochim Biophys Acta.; 1048: 93-9.
  • Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK. (2002) Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6. J Biol Chem.; 277: 11802-10.
  • Zakeri ZF, Wolgemuth DJ, Hunt CR. (1988) Identification and sequence analysis of a new member of the mouse HSP70 gene family and characterization of its unique cellular and developmental pattern of expression in the male germ line. Mol Cell Biol.; 8: 2925-32.
Document Type
Publication order reference
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv50i2p535kz
Identifiers
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.