SPERMATOGONIAL TRANSPLANTATION

精原细胞移植

• 批准号: 6138815
• 负责人: MICHAEL D GRISWOLD
• 金额: $ 21.13万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138815
• 关键词: Sertoli cells; androgen receptor; cell cell interaction; cell transplantation; embryo /fetus tissue /cell culture; gene expression; germ cells; laboratory mouse; laboratory rat; male; organ culture; sperm; spermatogenesis; stem cells; testis; tissue /cell culture; vitamin A deficiency; xenotransplantation

This application is from two experienced investigators who propose to utilize the newly developed technology of spermatogonial transplantation to answer fundamental questions in the field of male reproduction. The first two aims are to perform experiments which are a necessary prerequisite to eventual modification of the germ cell genome. We will utilize the vitamin A deficient rats and mice and prenatal and early postnatal mice as sources for undifferentiated spermatogonia for transplantation and cell culture. The spermatogonia will be transplanted into recipients of the same species (syngeneic-mouse to mouse or rat to rat) or another species (xenogeneic-rat to mouse or mouse to rat) before or after cell cultures. In the third aim, the analysis of the xenogeneic spermatogonial transplants will answer fundamental questions about the interactions between germ cells and Sertoli cells during spermatogenesis. For example, the cell type that controls the progression through or the timing of germ cell development can be determined after autoradiographic analysis of the xenogeneic transplants. The fourth aim involves experiments using testicular feminized or androgen insensitive strains of mice in transplantation experiments to answer long standing questions about the role of androgens in germ cell development. Overall, the transplantation model offers a new approach to answering questions about the fundamental control of spermatogenesis which have eluded investigators for many years. It also allows us to perform the initial steps necessary to modify the germ cell genome.

该申请由两位经验丰富的研究人员提出，他们提出利用新开发的精原细胞移植技术来回答男性生殖领域的基本问题。前两个目标是进行实验，这是最终修改生殖细胞基因组的必要先决条件。我们将利用维生素A缺乏的大鼠和小鼠以及产前和产后早期小鼠作为未分化精原细胞的来源，用于移植和细胞培养。在细胞培养之前或之后，精原细胞将被移植到同一物种（同系小鼠到小鼠或大鼠到大鼠）或另一个物种（异种小鼠到小鼠或小鼠到大鼠）的受体中。第三个目标是，对异种精原细胞移植的分析将回答有关精子发生过程中生殖细胞和支持细胞之间相互作用的基本问题。例如，控制生殖细胞发育进展或时间的细胞类型可以在异种移植物的放射自显影分析后确定。第四个目标涉及在移植实验中使用睾丸女性化或雄激素不敏感品系的小鼠进行实验，以回答有关雄激素在生殖细胞发育中的作用的长期存在的问题。总体而言，移植模型提供了一种新方法来回答多年来研究人员一直困惑的精子发生基本控制问题。它还允许我们执行修改生殖细胞基因组所需的初始步骤。