HST-1/FGF-4 protects male germ cells from apoptosis under heat-stress condition

被引:25
|
作者
Hirai, K
Sasaki, H
Yamamoto, H
Sakamoto, J
Kubota, Y
Kakizoe, T
Terada, M
Ochiya, T
机构
[1] Natl Canc Ctr, Res Inst, Sect Studies Metastasis, Tokyo 1040045, Japan
[2] Yokohama City Univ, Dept Urol, Kanazawa, Ishikawa 2360004, Japan
[3] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 1040045, Japan
[4] Natl Canc Ctr, Natl Canc Ctr, Res Inst, Tokyo 1040045, Japan
关键词
HST-1/FGF-4; spermatogenesis; apoptosis; testis; sertoli cell; lactate;
D O I
10.1016/j.yexcr.2003.11.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Apoptosis plays an important role in controlling the number of male germ cells and eliminating defective germ cells during testicular development and spermatogenesis. We show here that fibroblast growth factor-4 (HST-1/FGF-4) may play a critical role as a survival factor for genii cells, protecting them from apoptosis. Testes of adult male mice that received an adenovirus carrying human HST-1/FGF-4 (AxHST-1) or a control adenovirus (AxCAwt) were exposed to mild hyperthermia, which causes germ cell apoptosis. An in situ terminal-deoxynucleotidyl transferase-mediated deoxy-UTP nick end-labeling (TUNEL) assay characterized germ cell apoptosis. The results indicated that HST-1/FGF-4 significantly reduced the apoptotic death of germ cells and prevented testicular weight loss and sperm count reduction. We also found that Hst-1/Fgf-4 present in testes is up-regulated in vivo when the testes are exposed to mild hyperthermia, and that endogenous Hst-1/Fgf-4 mRNA expression in Sertoli cells are also induced when the cells are exposed to mild hyperthermia in vitro. In addition, the MAPK cascade, which could increase an FGF-dependent survival signal, is activated by HST-1/FGF-4 stimuli in germ cells. On the other hand, upon HST-1/FGF-4 stimulation, lactate production from Sertoli cells were induced, which is indispensable nutrient for germ cell survival. These results suggest that HST-1/FGF-4 can act as an important physiological anti-apoptotic factor for male germ cells in stimulating lactate production of Sertoli cells upon heat stress, thereby promoting germ cell survival. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:77 / 85
页数:9
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