Expression of Fas‐Fas Ligand in Murine Testis

Xu, Jimmy P.; Li, Xiang; Mori, Etsuko; Guo, Mao Wu; Matsuda, Ichiro; Takaichi, Hirohito; Amano, Takashi; Mori, Tsuneatsu

doi:10.1111/j.1600-0897.1999.tb00116.x

Cited by 27 publications

(19 citation statements)

References 45 publications

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“…In fact, in this model complete spermatogenesis was restored (after varying times depending on the amount of X-rad used), which indicates that stem cells remained functional and that the testis environment was normal. Recently, other authors have shown the presence of FasL mRNA in mouse Sertoli cells by ISH on paraffin-embedded sections (45). Our in situ data contradict this finding, but are in accordance with our parallel Northern blot and cytometric analyses results.…”

Section: Discussionsupporting

confidence: 91%

Testicular FasL is expressed by sperm cells

D’Alessio

Riccioli

Lauretti

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

131

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The testis is the main source of Fas ligand (FasL) mRNA in rodents; it is generally believed that this molecule, expressed on bordering somatic Sertoli cells, bestows an immune-privileged status in the testis by eliminating infiltrating inflammatory Fas-bearing leukocytes. Our results demonstrate that the attribution of testicular expression of FasL to Sertoli cells is erroneous and that FasL transcription instead occurs in meiotic and postmeiotic germ cells, whereas the protein is only displayed on mature spermatozoa. These findings point to a significant role of the Fas system in the biology of mammalian reproduction.testis ͉ immunoprivilege ͉ fertility

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Section: Discussionsupporting

confidence: 91%

Testicular FasL is expressed by sperm cells

D’Alessio

Riccioli

Lauretti

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

131

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“…Our study clearly shows that the increased susceptibility of stage VII to cell death is possibly a contribution of Fas-FasL interaction. The belief that Sertoli cells are the only source of FasL dominated thinking in testicular biology (12); however, in the recent past it has been shown that the spermatogenic cells have the ability to express both Fas and FasL (16). The presence of Fas-FasL in testicular cells has been linked to the ability of the testis to act as an immune privileged site and maintenance of testicular homeostasis by Sertoli cells eliminating spermatogenic cells.…”

Section: Discussionmentioning

confidence: 99%

“…As in other cells, male spermatogenic cells respond to external signals and to their internal milieu by activating intracellular signaling pathways that ultimately determine their fate. Signals that induce programmed cell death are known to initiate apoptotic pathways in spermatogenic cells involving members of the Bcl-2 family and also the Fas-FasL system (12). In FasL-induced spermatogenic cell death, it is generally accepted that FasL from Sertoli cells kill the spermatogenic cells by engaging the Fas receptors present on them.…”

mentioning

confidence: 99%

Diethylstilbestrol Induces Rat Spermatogenic Cell Apoptosis in Vivo through Increased Expression of Spermatogenic Cell Fas/FasL System

Nair

Shaha

2003

Journal of Biological Chemistry

106

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The significant role that estrogens play in spermatogenesis has opened up an exciting area of research in male reproductive biology. The realization that estrogens are essential for proper maintenance of spermatogenesis, as well as growing evidence pointing to the deleterious effects of estrogen-like chemicals on male reproductive health, has made it imperative to dissect the role estrogens play in the male. Using a model estrogen, diethylstilbestrol (DES), to induce spermatogenic cell apoptosis in vivo in the male rat, we provide a new insight into an estrogen-dependent regulation of the Fas-FasL system specifically in spermatogenic cells. We show a distinct increase in Fas-FasL expression in spermatogenic cells upon exposure to diethylstilbestrol. This increase is confined to the spermatid population, which correlates with increased apoptosis seen in the haploid cells. Testosterone supplementation is able to prevent DES-induced Fas-FasL up-regulation and apoptosis in the spermatogenic cells. DES-induced germ cell apoptosis does not occur in Fas-deficient lpr mice. One other important finding is that spermatogenic cells are type II cells, as the increase in Fas-FasL expression in the spermatogenic cells is followed by the cleavage of caspase-8 to its active form, following which Bax translocates to the mitochondria and precipitates the release of cytochrome c that is accompanied by a drop in mitochondrial potential. Subsequent to this, activation of caspase-9 occurs that in turn activates caspase-3 leading to the cleavage of poly(ADP-ribose) polymerase. Taken together, the data indicate that estrogen-like chemicals can precipitate apoptotic death in spermatogenic cells by increasing the expression of spermatogenic cell FasFasL, thus initiating apoptosis in the same lineage of cells through the activation of the apoptotic pathway chosen by type II cells.

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“…[8][9][10][11][12][13] Fas-FasL expression in the testis has been reported by various Authors. Fas has been shown to be expressed in both germ cells 11,14 and in Sertoli cells, 15,16 while FasL expression is more controversial mainly because of the lack of reliable specific antibodies. In fact some Authors report its expression in germ cells, 15,17 while others claim it is present in Sertoli cells.…”

Section: Introductionmentioning

confidence: 99%

“…In fact some Authors report its expression in germ cells, 15,17 while others claim it is present in Sertoli cells. 7,14,18,19 FasL has been reported to trigger germ-cell apoptosis, 6,7 even though the fine molecular events involved are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

FLIP is expressed in mouse testis and protects germ cells from apoptosis

et al. 2003

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Apoptosis control in adult testis is crucial to achieve normal spermatogenesis. In this study c-FLIP, an apoptosis-modulating protein, was investigated. In Western blot and immunohistochemical analyses, the 55 KDa c-FLIP long isoform (c-FLIP L ) was found to be expressed strongly in spermatocytes and spermatids, at low levels in spermatogonia and at almost undetectable levels in Sertoli cells. This expression pattern was confirmed by Northern blot analyses. Further experiments carried out on GC-1spg germ cell line revealed that reducing c-FLIP L expression increases Fas-dependent apoptosis. Conversely, restoring c-FLIP L expression reduces this response to control levels. Caspase-10 expression was found to match c-FLIP L expression pattern; further, caspase-10 activation upon anti-Fas treatment inversely correlated with c-FLIP L expression. Finally, TUNEL staining of seminiferous tubules incubated with anti-Fas antibody showed that apoptosis occurs mostly in basally located germ cells, indicating that such cells, expressing low levels of c-FLIP L , are sensitive to Fas-mediated apoptosis. These data indicate for the first time that c-FLIP L might control germ cell apoptosis and caspase activity in the adult testis.

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Expression of Fas‐Fas Ligand in Murine Testis

Abstract: Fas-FasL system seemed to play an apoptotic role in spermatogenesis by the molecular interaction between FasL on Sertoli cells and Fas on germ cells.

Cited by 27 publications

References 45 publications

Testicular FasL is expressed by sperm cells

Testicular FasL is expressed by sperm cells

Diethylstilbestrol Induces Rat Spermatogenic Cell Apoptosis in Vivo through Increased Expression of Spermatogenic Cell Fas/FasL System

FLIP is expressed in mouse testis and protects germ cells from apoptosis

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