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A research on the character and the specific gene expression of spermatogonial stem cells

精原干细胞的特性及特异性基因表达的研究

基本信息

批准号：
12670025
负责人：
SAWADA Hajime
金额：
$ 1.22万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670025/
关键词：
Spermatogonia Transplantation Leuprorelin Gonadotropin Teststerone c-Kit Stem cell factor 精祖細胞精巣 GFP 再生分化 GnRH

项目摘要

Male germ cells were isolated from donor mice, and successfully transplanted in mice devoid of germ cells. By using GFP transgenic mice as donors, transplanted germline stem cells could be distinguished from the cells of recipients, and their mode of expansion were traced under a fluorscent microscope. Three weeks after transplantation, most of the transplanted cells were undifferentiated spermatogoniae megative to c-Kit antibody, and formed distinct colonies. Later, more differentiated cells such as differentiated spermatogoniae and spermatocytes appeared in the colony.With this transplantation system, we ingestigated the effect of a gonadotropin antagonist, leuprorelin, which suppresses the secretion of gonadotropin from the pituitary and thus raise the intratesticular production of testosterone.When leuprorelin was adiministered, donor-derived colonies increased in size, showing the activation of growth of spermatogonial stem cells by leuprorelin. This indicates the inhibitory effect of testosterone in the process of spermatogonial growth, which is in contrast to the widely-accepted notion that testosterone is necessary for the survival and differentiation of germ cells after the meiotic stage.In search for the mechanism of leuprorelin inhibition, we hypothesized that stem cell factor/c-Kit signalling system has the highest possibility, and investigated the effect of leuprorelin in Sl/Sl mutant mice which do not express stem cell factor. The donor derived colonies, however, were formed in the Sl/Sl recipeint testes without any detrimental effect. We concluded that leuprorelin showed its effect on spermatogoniae through signalling mechanisms other than SCF/c-Kit.

从供体小鼠中分离出雄性生殖细胞，并成功移植到缺乏生殖细胞的小鼠体内。通过使用GFP转基因小鼠作为供体，移植的生殖干细胞可以与受体细胞区分开来，并在荧光显微镜下追踪它们的扩增模式。移植后三周，大多数移植细胞是对c-Kit抗体具有巨噬细胞活性的未分化精原细胞，并形成明显的集落。后来，集落中出现了更多分化的细胞，如分化的精原细胞和精母细胞。通过该移植系统，我们摄入了促性腺激素拮抗剂亮丙瑞林的作用，它抑制垂体促性腺激素的分泌，从而提高睾丸内睾酮的产生。当给予亮丙瑞林时，供体来源的集落大小增加，表明亮丙瑞林激活了精原干细胞的生长。这表明睾酮在精原细胞生长过程中具有抑制作用，这与人们广泛接受的认为睾酮是减数分裂期后生殖细胞的生存和分化所必需的观点相反。在寻找亮丙瑞林抑制机制的过程中，我们假设干细胞因子/c-Kit信号系统可能性最高，并研究了亮丙瑞林在Sl/Sl中的作用不表达干细胞因子的突变小鼠。然而，来自供体的集落在Sl/Sl配方睾丸中形成，没有任何有害作用。我们得出结论，亮丙瑞林通过 SCF/c-Kit 以外的信号传导机制显示其对精原细胞的影响。