RPG:Role of the Fas Antigen and Bcl-2 in Ovarian Follicular Apoptosis

RPG:Fas抗原和Bcl-2在卵巢卵泡细胞凋亡中的作用

• 批准号: 9306483
• 负责人: Susan Quirk
• 金额: $ 1.8万
• 依托单位: Health Research Incorporated/New York State Department of Health
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9306483&HistoricalAwards=false
• 关键词: RPG; Role; Fas; Antigen; Bcl

This is a research planning grant for women. Follicles in the ovary undergo a continuous process of growth and regression; only a small minority actually proceed to ovulation. Substantial evidence suggests that atresia occurs by the process of apoptosis, or programmed cell death. However, the genes controlling apoptosis are not known. The operating hypothesis of this research is that ovarian follicular apoptosis occurs in response to definable signals: either lack of a survival factor or induction by a cytotoxic stimulus. Genes coding for two proteins, the fas antigen and BCL-2, have been demonstrated to be intimately involved in apoptosis in other systems, inducing and suppressing the process, respectively. Limited data available indicate that the fas antigen is expressed in the mouse ovary and bcl-2 is expressed in the chicken ovary. The proposed preliminary research will examine the role of these genes in ovarian follicular apoptosis by studying their expression in vivo in healthy and atretic follicles of rats. Subsequent research will examine the regulation of expression of the fas antigen and bcl-2 in rat follicular cells in vitro by various mediators of follicular development. Finally, a potential cause and effect relationship between fallicular atresia and expression of these genes will be examined by inhibiting the activity or expression of the gene products using antibodies and antisense oligonucleotides to mRNA. Mammalian females are born with a full complement of germ cells, the oocytes, present in the ovary. Oocytes become surrounded by a structure called the follicle which is comprised of granulosa and theca cells. Throughout life ovarian follicles are stimulated to develop, a process involving growth and differentiation of all cell types within the follicle. Only a few of the follicles that enter the growing pool actually progress to ovulation. The vast majority begin to degenerate, or undergo atresia at different points in the developmental process. Recent evidence indicates that ovarian follicular atresia occurs by programmed cell death, an active process whereby a cell mediates its own death by following a genetically determined developmental program. Factors regulating cell death in the ovary have not been identified. This propossal will test whether genes encoding two proteins, the fas antigen and BCL-2, which are involved in inducing and suppressing programmed cell death in other systems (the immune system, nervous system and in various tumor cells) also regulate cell death in the ovary. An understanding of follicular degeneration is essential to allow development of improved methods of fertility control, treatment of infertility and enhancement of fertility. There is intense interest in programmed cell death because of its involvement in a wide variety of normal developmental processes as well as its relevance to the development of cancers. The ovary provides an excellent model for the study of programmed cell death.

这是一项针对妇女的研究规划补助金。 卵泡 子房经历一个连续的生长和退化过程;只有 只有一小部分会排卵 实质性 证据表明闭锁通过凋亡过程发生， 或者程序性细胞死亡 然而，控制细胞凋亡的基因 不知道。 这项研究的操作假设是， 卵巢滤泡细胞凋亡的发生是对可定义的 信号：缺乏生存因子或诱导 细胞毒性刺激 编码两种蛋白质fas抗原的基因 和BCL-2，已被证明与 其他系统中的细胞凋亡，诱导和抑制该过程， 分别 有限的数据表明fas抗原 在小鼠卵巢中表达，而bcl-2在 鸡卵巢 拟议的初步研究将审查 这些基因在卵巢卵泡凋亡中的作用， 它们在大鼠健康和闭锁卵泡中的体内表达。 随后的研究将检查表达的调节， 体外培养大鼠卵泡细胞Fas抗原和Bcl-2的表达 卵泡发育的各种介质。 最后，一个潜在的 胎儿先天性闭锁与 这些基因的表达将通过抑制 使用抗体测定基因产物的活性或表达， 反义寡核苷酸。 哺乳动物雌性生来就有完整的生殖细胞， 卵母细胞，存在于卵巢中。 卵母细胞被 一种叫做卵泡的结构，由颗粒层和 泡膜细胞 在人的一生中，卵泡受到刺激， 发育，涉及所有细胞生长和分化的过程 毛囊内的类型。 只有少数进入的卵泡 生长池实际上进展到排卵。 绝大多数 开始退化，或在不同的点进行闭锁， 发展过程 最近的证据表明，卵巢 卵泡闭锁是由程序性细胞死亡引起的， 一个细胞通过遵循一个过程来介导自身死亡的过程。 基因决定的发育程序 调节因素 卵巢中的细胞死亡尚未确定。 这个提议 将测试编码两种蛋白质的基因，fas抗原和 BCL-2，其参与诱导和抑制程序化的 其他系统（免疫系统、神经系统和 在各种肿瘤细胞中）也调节卵巢中的细胞死亡。 一个 了解卵泡退化是必不可少的， 制定更好的生育控制方法，治疗 不孕症和提高生育能力。 有强烈的 对程序性细胞死亡感兴趣，因为它参与了一个 各种各样的正常发育过程，以及其 与癌症发展的相关性。 卵巢提供了一个 这是研究程序性细胞死亡的极好模型。