title: Testis atrophy and reduced sperm motility in transgenic mice overexpressing c-FLIP(L).
abstract: 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.
authors.affiliation: Department of Histology and Medical Embryology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Antonangeli
authors.forename: Simonetta
authors.initials: S
authors.lastname: Petrungaro
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Coluccia
authors.forename: Antonio
authors.initials: A
authors.lastname: Filippini
authors.forename: Elio
authors.initials: E
authors.lastname: Ziparo
authors.forename: Claudia
authors.initials: C
authors.lastname: Giampietri
mesh_terms: 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
chemical_list: 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