Apoptosis is a key mechanism in spermatogenesis, and in testis, most gonocytes degenerate at fetal and postnatal ages to select a cell subset committed to become germ stem cells. The aim of the present study is to investigate mechanisms controlling the massive apoptosis of fetal gonocytes. We evaluated the expression and function of c-Flip, an apoptosis inhibitor known to interfere with the proapoptotic Fas-signaling pathway in a variety of cell types, but never investigated in fetal testis. Expression of c-Flip long isoform (c-FlipL) within fetal testis was localized in gonocytes at 16.5 and 18.5 days post coitum (dpc), both at the mRNA and protein level, while it was weakly expressed or undetectable at earlier stages. Moreover, Fas protein was found in fetal testes at 13.5, 16.5, and 18.5 dpc. Testes at 18.5 dpc, expressing high levels of c-FlipL, were resistant to Fas-induced apoptosis while they became highly sensitive when c-FlipL was inhibited by antisense c-Flip oligos. In addition, there was an inverse relation between gonocyte spontaneous apoptosis sensitivity and c-FlipL levels. Furthermore, caspase-10 activity was inversely related with c-FlipL expression, suggesting that caspase-10 might be a target of c-FlipL. These data represent the first evidence demonstrating c-Flip expression in fetal testes and its role in protecting gonocytes from Fas-dependent apoptosis.

Giampietri, C., Petrungaro, S., Klinger, F.g., Coluccia, P., Paone, A., Vivarelli, E., et al. (2006). c-Flip expression and function in fetal mouse gonocytes. THE FASEB JOURNAL, 20(1), 124-6 [10.1096/fj.05-4626fje].

c-Flip expression and function in fetal mouse gonocytes

KLINGER, FRANCESCA GIOIA;DE FELICI, MASSIMO;
2006-01-01

Abstract

Apoptosis is a key mechanism in spermatogenesis, and in testis, most gonocytes degenerate at fetal and postnatal ages to select a cell subset committed to become germ stem cells. The aim of the present study is to investigate mechanisms controlling the massive apoptosis of fetal gonocytes. We evaluated the expression and function of c-Flip, an apoptosis inhibitor known to interfere with the proapoptotic Fas-signaling pathway in a variety of cell types, but never investigated in fetal testis. Expression of c-Flip long isoform (c-FlipL) within fetal testis was localized in gonocytes at 16.5 and 18.5 days post coitum (dpc), both at the mRNA and protein level, while it was weakly expressed or undetectable at earlier stages. Moreover, Fas protein was found in fetal testes at 13.5, 16.5, and 18.5 dpc. Testes at 18.5 dpc, expressing high levels of c-FlipL, were resistant to Fas-induced apoptosis while they became highly sensitive when c-FlipL was inhibited by antisense c-Flip oligos. In addition, there was an inverse relation between gonocyte spontaneous apoptosis sensitivity and c-FlipL levels. Furthermore, caspase-10 activity was inversely related with c-FlipL expression, suggesting that caspase-10 might be a target of c-FlipL. These data represent the first evidence demonstrating c-Flip expression in fetal testes and its role in protecting gonocytes from Fas-dependent apoptosis.
gen-2006
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/17 - ISTOLOGIA
English
Con Impact Factor ISI
Male; Caspases; Testis; Animals; Receptors, Tumor Necrosis Factor; CASP8 and FADD-Like Apoptosis Regulating Protein; Apoptosis; Intracellular Signaling Peptides and Proteins; Fetus; Signal Transduction; Gene Expression Regulation, Developmental; Mice; Antigens, CD95; Caspase 10
Giampietri, C., Petrungaro, S., Klinger, F.g., Coluccia, P., Paone, A., Vivarelli, E., et al. (2006). c-Flip expression and function in fetal mouse gonocytes. THE FASEB JOURNAL, 20(1), 124-6 [10.1096/fj.05-4626fje].
Giampietri, C; Petrungaro, S; Klinger, Fg; Coluccia, P; Paone, A; Vivarelli, E; Filippini, A; De Cesaris, P; DE FELICI, M; Ziparo, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/66016
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