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.
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.
Widłak
Wiesława
W
Department of Tumor Biology, Center of Oncology, Maria Skłodowska-Curie Memorial Institute, 44-100 Gliwice, Poland. wwidlak@io.gliwice.pl
Benedyk
Konrad
K
Vydra
Natallia
N
Głowala
Magdalena
M
Scieglińska
Dorota
D
Małusecka
Ewa
E
Nakai
Akira
A
Krawczyk
Zdzisław
Z
D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005854:Germ Cells / Q000166:cytology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D000076249:Heat Shock Transcription Factors; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012670:Seminiferous Epithelium / Q000473:pathology* / Q000648:ultrastructure; D013090:Spermatocytes / Q000378:metabolism; D013737:Testis / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors; D019076:Transgenes / Q000235:genetics
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors