Testis atrophy and reduced sperm motility in transgenic mice overexpressing c-FLIPL

ObjectiveTo study the effect of c-FLIP overexpression in testicular germ cells.DesignA novel transgenic mouse model overexpressing the apoptotic modulator c-FLIP in the testis was generated.SettingAnimal facility and university research laboratory.Animal(s)Transgenic mice overexpressing the long isoform of c-FLIP (c-FLIPL) 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.ResultsStra8 promoter was found to activate the ectopic overexpression of c-FLIPL 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-FLIPL 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.