Dysfunctional spermatogenesis in transgenic mice overexpressing bHLH-Zip transcription factor, Spz1

被引:32
|
作者
Hsu, SH
Hsieh-Li, HM
Li, H [1 ]
机构
[1] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan
[2] Natl Taiwan Normal Univ, Dept Life Sci, Taipei 116, Taiwan
[3] Taipei Med Univ, Grad Inst Med Sci, Taipei 110, Taiwan
[4] Natl Yang Ming Univ, Dept Biochem, Taipei 112, Taiwan
关键词
Spz1; dysfunctional spermatogenesis; apoptosis; Fas/FasL;
D O I
10.1016/j.yexcr.2003.10.029
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Spz1, a previously identified basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor, is expressed specifically in the testis and epididymis of adult mice. However, Spz1's in vivo function is unclear. To study the function of Spz1 in vivo, we established Spz1 transgenic mice. Using this model, we were able to demonstrate that overexpression of Spz1 in the testis destroys tissue homeostasis at an early stage of spermatogenesis, which in turn induces apoptosis in germ cells and thus reduces male fertility. We identified that Spz1 is ectopically expressed in multiple tissues of transgenic male mice by Western blot analysis. In the testes of transgenic mice, Spz1 proteins were found to be overexpressed in both germ and somatic cells as determined by immuno fluorescence staining. This upregulated cell proliferation was confirmed by in vivo BrdU incorporation in multinucleated gonocytes of 1-week-old transgenic mice. However, histological and immunohistochemical analyses indicated that these multinucleated germ cells in seminiferous tubules subsequently underwent apoptosis at 2 and 4 weeks of age through Fas/FasL- and ER stress-signaling pathways. Furthermore, germ cells surviving two cycles of meiosis suffered aberrant spermiogenesis, generating a large pool of abnormal spermatozoa. The transgenic male mice with reduced populations of normal spermatozoa produced offsprings of smaller litter sizes and became infertile at 6 months of age. These results suggest that cell proliferation in early spermatogenesis is critically regulated by multisignal pathways and unregulated cell proliferation at this stage, as induced by Spz1, leads to germ cell apoptosis. These results imply that Spz1 plays an important regulatory role during spermatogenesis. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:185 / 198
页数:14
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