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.
DESIGN: A novel transgenic mouse model overexpressing the apoptotic modulator c-FLIP in the testis was generated.
SETTING: Animal facility and university research laboratory. ANIMAL(S): 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. INTERVENTION(S): Spermatozoa motility and testis histological, immunohistochemical, and Western blot analyses were carried out in transgenic and control derived specimens. MAIN OUTCOME MEASURE(S): 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. CONCLUSION(S): 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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.