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

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• 作者：Fabrizio Antonangeli ; Simonetta Petrungaro ; Pierpaolo Coluccia ; Antonio Filippini ; Elio Ziparo ; Claudia Giampietri
• 关键词：Apoptosis ; c-FLIP ; germ cells ; spermatogenesis ; Stra8 ; testis atrophy ; transgenic mouse
• 刊名：Fertility and Sterility
• 出版年：2010
• 出版时间：15 March 2010
• 年：2010
• 卷：93
• 期：5
• 页码：1407-1414
• 全文大小：1480 K

文摘

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.