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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 黄体是排卵后源自卵泡的短暂内分泌腺；该腺体是类固醇激素黄体酮的主要来源，黄体酮对于哺乳动物宫内妊娠的建立和维持至关重要。 因此，了解控制黄体功能寿命的过程与控制生育力和治疗某些类型的不孕症直接相关。 有证据表明，程序性细胞死亡或细胞凋亡的过程与许多物种的黄体退化有关，但黄体细胞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（caspases -2、-3、-8和-9）在大鼠黄体生命周期中动情周期的变化；怀孕; (2)评价黄体分解激素前列腺素F2α对这些促凋亡基因的调节作用； (3)确定抗凋亡剂1-磷酸鞘氨醇(S1P)是否会阻止半胱天冬酶激活和黄体黄体溶解。 此外，Notch 信号通路在黄体溶解的进展中也起着关键作用。拟议研究的结果将有助于设计关键的比较研究，以确定这些细胞凋亡途径与灵长类 CL 以及最终黄体功能障碍的临床综合征的相关性。