Involvement of Fas in the apoptosis of mouse germ cells induced by experimental cryptorchidism

Ogi, Shinsuke; Tanji, Nozomu; Yokoyama, M.; Takeuchi, Masafumi; Terada, Nobuyuki

doi:10.1007/s002400050017

Cited by 39 publications

(32 citation statements)

References 17 publications

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“…2 In the study of Tomomasa et al 13 on TS inbred rats (congenitally cryptorchid rat), 70% of which have cryptorchidism at birth, the weight of the affected testis was decreased significantly at the 4 th , 6 th and 8 th weeks, and spermatogenesis was decreased as well. In their experimental study, Ogi et al 14 showed that testicular weight was decreased to 23% and 31% on the 4 th and 7 th days, respectively. In the present experimental study, both testes were found to continue growing where the weight of the left testis was less than that of the right one.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

Dündar

Koçak

Çulhacı

et al. 2005

Pathol. Oncol. Res.

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Section: Discussionmentioning

confidence: 96%

“…13 In another study, seminiferous tubules containing apoptotic cells were more intensive in undescended testes. 14 In a clinical study on patients with cryptorchidism, Heiskanen et al 1 identified spermatogonia as the main apoptotic cell type in the seminiferous tubules. Apoptosis was shown only in a few Sertoli cells.…”

Section: Discussionmentioning

confidence: 99%

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

Dündar

Koçak

Çulhacı

et al. 2005

Pathol. Oncol. Res.

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“…10 We investigated whether Fas is involved in these events because we and other groups previously showed the expression of Fas in both male and female gonads. [31][32][33][34][35][36][37][38]41,[43][44][45][46] To clarify whether Fas is involved in germ cell degeneration in the gonads of W mutant mice, we generated double-mutant mice (W v /W v :Fas À/À ) by intercrossing the spontaneous Kit mutant W v mice with Fas-deficient mice against the same C57BL/6 background.…”

Section: Analysis Of Double-mutant Micementioning

confidence: 99%

“…[41][42][43] In addition, Fas expression was shown to increase in the testes after drug treatment, ischemia-reperfusion or heat shock. [44][45][46][47] In these damaged testes, Fas may play a role as a regulator of pathological germ cell death, although this has not been clearly determined.…”

Section: Introductionmentioning

confidence: 99%

Involvement of death receptor Fas in germ cell degeneration in gonads of Kit-deficient Wv/Wv mutant mice

et al. 2003

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Kit and its ligand stem cell factor (SCF) play a fundamental role in hematopoiesis, melanogenesis and gametogenesis. Homozygous W v mutant mice with a mutation in kit show abnormalities in these cell lineages. Fas is a member of the death receptor family inducing apoptosis. In this study, we generated double-mutant mice (W v /W v :Fas À/À ) and analyzed histologically their reproductive organs. In testes and ovaries of the double-mutant mice, testicular germ cells and oocytes were detected, respectively, whereas the same-aged W v /W v mice contained neither cells. In addition, inhibition of Kit signals by administration of anti-Kit mAb, which induces degeneration of testicular germ cells in vivo in wild-type mice, did not cause degeneration in Fas-deficient mice. In testicular germ cells of W v /W v mutant mice, an increase of Fas expression was observed in spermatogonia. Further, in vitro treatment with SCF was shown to downregulate Fas on fibroblasts expressing exogenous Kit through activation of PI3-kinase/Akt. All the results clearly indicate that Fasmediated apoptosis is involved in germ cell degeneration accompanied by defects in Kit-mediated signals, and Kit signaling negatively regulates Fas-mediated apoptosis in vivo.

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“…However, there has been no direct evidence indicating that Fas is responsible for testicular germ cell apoptosi s, because germ cell apoptosis is not inhibited in lpr/lpr and gld/gld mice that have mutations in the Fas and the Fas! genes, respectively (Ohta et al, 1996;Lee et al , 1997;Ogi et al , 1998). A report has al so argued that Fas and Fas!…”

mentioning

confidence: 99%

p53 and Fas Are Sequential Mechanisms of Testicular Germ Cell Apoptosis

Yin

Stahl

DeWolf

et al. 2002

Journal of Andrology

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Testicular germ cell apoptosis in the cryptorchid testis is induced by abdominal heat stress. p53-dependent apoptosis appears responsible for the initial phase of germ cell loss in experimental cryptorchidism based on a 3-day delay of apoptosis in ps3-1 -mice. However, the mechanisms underlying the subsequent p53-independent apoptosis have not been identified. Although studies have suggested that Fas plays a role in testicular germ cell apoptosis, no direct evidence has been shown. To test the hypothesis that Fas is involved in testicular germ cell apoptosis and is responsible for the p53-independent phase of apoptosis in the cryptorchid testis, pS3-1 -, lpr/lpr (a spontaneous mutation in the Fas gene, which causes autoimmune disease) double-mutant mice were generated and unilateral cryptorchidism was induced in these mice. It was found that A poptosis plays an important role in testicular germ cell development, and appears to be the shared responsible mechanism for male infertility (Richburg, 2000) caused by testicular exposure to elevated temperature (VanDemark and Free, 1970), toxicants (Richburg, 2000), radiation (Grossfeld and Small, 1998), chemotherapy (Costabile and Spevak, 1998), hormonal depletion (Sinha Hikim and Swerdloff, 1999), and torsion (Turner et al, 1997). It has been known since the 1920s that infertility associated with cryptorchidism, a birth disorder of undescended testes affecting I% of newborn boys (Jensen et al, 1995), is due to germ cell loss caused by testicular exposure to abdominal temperature (Fukui , 1923;Frankenhuis and Wensing, 1979). By using a mouse model of experimental cryptorchidism, it has been shown that a p53-dependent pathway is responsible for the initial phase of germ cell loss by apoptosis from day 7 to day 9 following exposure of the testis to abdominal temperature, and subsequent apoptosis involves an unknown p53-independent pathway (Yin et al, 1998).Fas and Fas ligand (Fas!) interaction is a major apoptotic mechanism found in various tissues and cell types , and studies have suggested that Fas is expressed in germ 64testicular weight reduction and germ cell apoptosis were delayed by an additional 3 days, and the Fas production increased in the time frame of p53-independent apoptosis in the experimental cryptorchid testis of wild-type mice. These results suggest that Fas is involved in testicular germ cell apoptosis, and that Fas-dependent apoptosis is responsible for the p53-independent phase of germ cell apoptosis in the cryptorchid testis. The cascade of testicular germ cell apoptosis in response to heat stress implies the existence of sequential quality control mechanisms in spermatogenesis.

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Involvement of Fas in the apoptosis of mouse germ cells induced by experimental cryptorchidism

Cited by 39 publications

References 17 publications

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

Involvement of death receptor Fas in germ cell degeneration in gonads of Kit-deficient Wv/Wv mutant mice

p53 and Fas Are Sequential Mechanisms of Testicular Germ Cell Apoptosis

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