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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 叶黄素是一种瞬时内分泌腺，排卵后源自卵巢卵泡。该腺是类固醇激素孕酮的主要来源，这对于在哺乳动物的宫内妊娠建立和维持至关重要。 因此，了解控制曲目功能寿命的过程的知识与控制生育能力和治疗某些类型的不孕症直接相关。 有证据表明，称为编程细胞死亡或凋亡的过程与许多物种的黄体消退有关，但是在黄体凋亡期间发生的调节和分子机制尚不清楚。 因此，该项目的具体目的是：（1）确定在发情周期和妊娠中大鼠corpus luteum的使用寿命中促凋亡基因（caspase -2，-3，-8和-9）的变化； （2）评估叶酸激素前列腺素F2α对这些促凋亡基因的调节； （3）确定抗凋亡剂1-磷酸鞘氨醇（S1P）是否会防止叶酸菌群的胱天冬酶激活和黄体溶解。 同样，Notch信号通路在黄体溶解的进程中具有关键作用。拟议研究的结果将促进批判性比较研究的设计，以确定这些凋亡途径与灵长类动物CL的相关性，最终是黄体功能障碍的临床综合症。