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.

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.