Testis atrophy and reduced sperm motility in transgenic mice overexpressing c-FLIPL
Received 17 October 2008; received in revised form 28 November 2008; accepted 7 January 2009. published online 16 March 2009.
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-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.
Results
Stra8 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.
aDepartment of Histology and Medical Embryology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy
bDepartment of Surgery, P. Valdoni, Sapienza University of Rome, Rome, Italy
Reprint requests: Claudia Giampietri, Ph.D., Department of Histology and Medical Embryology, Sapienza University of Rome, via A. Scarpa 14, 00161 Rome, Italy (FAX: 39-064462854).
F.A. has nothing to disclose. S.P. has nothing to disclose. P.C. has nothing to disclose. A.F. has nothing to disclose. E.Z. has nothing to disclose. C.G. has nothing to disclose.
This work was supported by grants from Ministero dell' Università e della Ricerca Scientifica e Tecnologica, PRIN 2007.
ABSTRACT