Testis atrophy and reduced sperm motility in transgenic mice overexpressing c-FLIP(L).
OBJECTIVE
To study the effect of c-FLIP overexpression in testicular germ cells.


METHODS
A novel transgenic mouse model overexpressing the apoptotic modulator c-FLIP in the testis was generated.


METHODS
Animal facility and university research laboratory.


METHODS
Transgenic mice overexpressing the long isoform of c-FLIP (c-FLIP(L)) under the transcriptional control of a 400 bp long regulatory region of the Stra8 promoter.


METHODS
Spermatozoa motility and testis histological, immunohistochemical, and Western blot analyses were carried out in transgenic and control derived specimens.


METHODS
Testis morphology, sperm motility, and germ cell apoptosis were assayed.


RESULTS
Stra8 promoter was found to activate the ectopic overexpression of c-FLIP(L) in round and elongated spermatids. As a consequence of such overexpression, a dramatic loss of germ cells was observed, resulting in testicular atrophy associated with reduced sperm motility.


CONCLUSIONS
The data show that c-FLIP(L) forced expression in haploid male germ cells has detrimental effects on spermatogenesis and sperm quality and reveal a possible mechanism underlying the onset of testicular atrophy.
Antonangeli
Fabrizio
F
Department of Histology and Medical Embryology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
Petrungaro
Simonetta
S
Coluccia
Pierpaolo
P
Filippini
Antonio
A
Ziparo
Elio
E
Giampietri
Claudia
C
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D013081:Sperm Motility; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D011506:Proteins; C102019:Stra8 protein, mouse; C505526:Casp8 protein, mouse; D053181:Caspase 8