REGULATION AND ROLE OF APOPTOSIS IN CORPUS LUTEUM REGRESSION

细胞凋亡在黄体退化中的调节和作用

• 批准号: 8357759
• 负责人: RICHARD L STOUFFER
• 金额: $ 0.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357759
• 关键词: Apoptosis; Apoptotic; CASP2 gene; Caspase; Clinical; Comparative Study; Contraceptive methods; Dinoprost; Endocrine Glands; Estrous Cycle; Functional disorder; Funding; Genes; Gland; Grant; Hormones; Infertility; Knowledge; Longevity; Luteolysis; Maintenance; Mammals; Molecular; National Center for Research Resources; Notch Signaling Pathway; Ovarian Follicle; Ovulation; Pathway interactions; Pregnancy; Primates; Principal Investigator; Process; Progesterone; Rattus; Regulation; Research; Research Infrastructure; Resources; Role; Source; Syndrome; United States National Institutes of Health; corpus luteum; cost; design; prevent; sphingosine 1-phosphate; steroid hormone

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The corpus luteum is a transient endocrine gland derived from the ovarian follicle after ovulation; this gland is the primary source of the steroid hormone progesterone, which is essential for the establishment and maintenance of intrauterine pregnancy in mammals. Therefore, knowledge of the processes controlling the functional lifespan of the corpus luteum is directly relevant to controlling fertility and treating certain types of infertility. Evidence suggests that the process called programmed cell death or apoptosis is associated with luteal regression in many species, but the regulation and molecular mechanisms occurring during luteal apoptosis are unknown. Accordingly, the specific aims of this project are: (1) To determine the changes in the pro-apoptotic genes (caspases -2, -3, -8, and -9) during the lifespan of rat corpus luteum in the estrous cycle and pregnancy; (2) To evaluate the regulation of these pro-apoptotic genes by the luteolytic hormone prostaglandin F2 alpha; and (3) To determine whether the anti-apoptotic agent sphingosine-1-phosphate (S1P) will prevent caspase activation and luteolysis of the corpus luteum. Also, the Notch signaling pathway has a critical role in the progression of luteolysis. The results of the proposed studies will facilitate the design of critical comparative studies to determine the relevance of these apoptotic pathways to the primate CL, and ultimately, clinical syndromes of luteal dysfunction.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 黄体是排卵后从卵泡中产生的一过性内分泌腺，它是类固醇激素孕酮的主要来源，孕酮对哺乳动物宫内妊娠的建立和维持是必不可少的。因此，对控制黄体功能寿命的过程的了解直接关系到控制生育能力和治疗某些类型的不孕症。有证据表明，在许多物种中，被称为程序性细胞死亡或凋亡的过程与黄体退化有关，但黄体凋亡过程中发生的调节和分子机制尚不清楚。因此，本项目的具体目标是：(1)确定促凋亡基因(caspase-2、-3、-8和-9)在大鼠黄体发情周期和妊娠期间的变化；(2)评估黄体溶解激素前列腺素F2α对这些促凋亡基因的调节；以及(3)确定抗凋亡剂1-磷酸鞘氨醇(S1P)是否可以阻止半胱氨酸酶的激活和黄体的溶解。此外，Notch信号通路在黄体溶解的进程中起着关键作用。建议的研究结果将有助于设计关键的比较研究，以确定这些凋亡途径与灵长类CL，并最终与黄体功能障碍的临床症状的相关性。