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.

Widłak, Wiesława; Benedyk, Konrad; Vydra, Natallia; Głowala, Magdalena; Ścieglińska, Dorota; Małusecka, Ewa; Nakai, Asami; Krawczyk, Z

doi:10.18388/abp.2003_3706

Cited by 27 publications

(18 citation statements)

References 23 publications

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“…It has been previously observed that expression of this constitutively active form of HSF1 in spermatocytes of transgenic mice induces massive apoptosis (Nakai et al . 2000;Widlak et al . 2003a;Vydra et al .…”

Section: Active Hsf1 Down-regulates Hsp702 Expressionmentioning

confidence: 88%

“…However, hypothetical HSF1-dependent factor(s) involved in negative regulation of Hsp70.2/Hst70 and other testis-specific genes remain to be identified. Apparently, elimination of spermatocytes by apoptosis cannot contribute significantly to down-regulation of HSP70.2 detected in 18-day-old pHST-HSF1∆RD transgenic males because massive HSF1dependent apoptosis and degeneration of seminiferous epithelium are observed in older animals (Widlak et al 2003a;Vydra et al 2006).…”

Section: Discussionmentioning

confidence: 98%

“…Activation of HSF1 in spermatocytes does not activate inducible HSPs but leads instead to a massive caspase-3dependent apoptosis and degeneration of seminiferous tubules in testes of 3-week-old and older mice (Widlak et al 2003a;Vydra et al 2006). Here we demonstrate that HSF1-induced apoptosis is preceded by a marked down-regulation in Hsp70.2 gene expression, and that spermatocytes undergoing the terminal stages of apoptosis (DNA fragmentation) do not contain HSP70.2 protein.…”

Section: Discussionmentioning

confidence: 99%

“…To directly assess the role of HSF1 in regulating the Hsp70.2/Hst70 gene we have analyzed the levels of Hsp70.2 gene transcripts (by RT-PCR) and HSP70.2 proteins (by Western blot) in testes of either wild-type mice or transgenic mice expressing a constitutively active form of HSF1 (the pHST-HSF1 ∆ RD transgene). Because the Hsf1 transgene is under the control of the rat Hst70 promoter (Widlak et al . 2003a;Vydra et al .…”

Section: Active Hsf1 Down-regulates Hsp702 Expressionmentioning

confidence: 99%

“…Transcription of inducible Hsp70 genes is permanently blocked in spermatocytes and expression of constitutively active HSF1 in such cells leads to caspase-3 dependent apoptosis and male infertility (Nakai et al . 2000;Widlak et al . 2003a;Vydra et al .…”

Section: Introductionmentioning

confidence: 99%

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Heat shock transcription factor 1 down‐regulates spermatocyte‐specific 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes

Widłak¹,

Vydra²,

Małusecka³

et al. 2007

Genes to Cells

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Expression of constitutively active heat shock transcription factor 1 (HSF1) in mouse spermatocytes induces apoptosis and leads to male infertility. We report here that prior to the onset of massive apoptosis caused by expression of active HSF1 in spermatocytes a marked reduction in spermatocyte-specific Hsp70.2 mRNA and protein levels occurs. In addition, HSP70.2 protein relocalizes from a predominant cytoplasmic to a nuclear position in developing spermatocytes that express active HSF1. Later in the developmental stages, cells undergoing HSF1-induced apoptosis essentially lack the HSP70.2 protein. The down-regulation of Hsp70.2 gene expression by HSF1 is paradoxical because HSF1 is the prototypical activator of HSP genes. Furthermore, HSF1-mediated repression neither involved a heat shock element (HSE)-like sequence adjacent to the Hsp70.2 gene nor were Hsp70.2 promoter sequences associated directly with HSF1. Interestingly, other spermatocyte- and spermatid-specific transcripts are also down-regulated in testes of transgenic mice expressing active HSF1, suggesting involvement of a putative HSF1-dependent block of development of spermatogenic cells. Importantly however, transcription of the Hsp70.2 gene is down-regulated in testes of wild-type mice subjected to a hyperthermia that induces transient activation of HSF1, indicating that the spermatocyte-specific activity of HSF1 might misdirect a network of transcription factors required for proper regulation of Hsp70.2.

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Section: Active Hsf1 Down-regulates Hsp702 Expressionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Active Hsf1 Down-regulates Hsp702 Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Heat shock transcription factor 1 down‐regulates spermatocyte‐specific 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes

Widłak¹,

Vydra²,

Małusecka³

et al. 2007

Genes to Cells

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Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: Intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage‐gated channels, methylation/acetylation, and transcription factors

Hermo

Pelletier

Cyr

et al. 2009

Microscopy Res & Technique

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As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic.

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Expression of stress inducible protein 1 (Stip1) in the mouse testis

Mizrak¹,

Bogerd²,

López-Casas³

et al. 2006

Molecular Reproduction Devel

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Phthalate esters are considered endocrine disruptors that interfere with the endocrine balance and development of the mammalian testis. Mono-2-ethylhexyl phthalate (MEHP), the active metabolite of the ubiquitously used plasticizer di-2-ethylhexyl phthalate (DEHP), acts upon Sertoli cells as initial target. By subtractive cDNA libraries we identified genes deregulated as response to MEHP in primary cultures of mouse Sertoli cells. The expression of mouse stress inducible protein 1 (Stip1) was detected as upregulated as a result of MEHP exposure. Stip1 is a cochaperone protein that is homologous to the human heat shock cognate protein 70 (hsc70)/heat shock protein 90 (hsp90)-organizing protein (Hop). To assess the presence and localization of Stip1 in mouse testis and its potential role in stress defense, we studied the expression pattern of the Stip1 protein by immunohistochemistry and of the mRNA by in situ hybridization. Both the protein and the mRNA of Stip1 were mainly found in the cytoplasm of all types of spermatogonia and spermatocytes up till zygotene, the expression decreased during late pachytene and was very weak in diplotene spermatocytes and round spermatids. Interestingly, this expression pattern resembled the pattern of stress sensitivity of spermatogenic cells in that the most sensitive cell types show the weakest expression of Stip1. This suggests an important role for Stip1 in the ability of germ cells to survive in stress conditions including high temperatures.

show abstract

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.

Cited by 27 publications

References 23 publications

Heat shock transcription factor 1 down‐regulates spermatocyte‐specific 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes

Heat shock transcription factor 1 down‐regulates spermatocyte‐specific 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: Intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage‐gated channels, methylation/acetylation, and transcription factors

Expression of stress inducible protein 1 (Stip1) in the mouse testis

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