REGULATION AND ROLE OF APOPTOSIS IN CORPUS LUTEUM REGRESSION

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 黄体是一个短暂的内分泌腺，来自排卵后的卵泡;这个腺体是类固醇激素孕酮的主要来源，这是建立和维持哺乳动物宫内妊娠所必需的。 因此，了解控制黄体功能寿命的过程与控制生育和治疗某些类型的不孕症直接相关。 有证据表明，称为程序性细胞死亡或凋亡的过程与许多物种的黄体退化有关，但黄体凋亡过程中发生的调节和分子机制尚不清楚。 因此，本课题的具体目标是：（1）确定促凋亡基因的变化（2）评估促凋亡基因在促黄体生成激素前列腺素F2 α（PGF 2 α）作用下的表达;以及（3）确定抗凋亡剂鞘氨醇-1-磷酸（S1 P）是否会阻止半胱天冬酶激活和黄体溶解。 拟议的研究的结果将有利于关键的比较研究，以确定这些凋亡途径的灵长类动物CL的相关性，并最终，黄体功能障碍的临床综合征的设计。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. 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.