Ovulation and Luteal Formation in Rodents Monkeys and Women

描述（由申请人提供）：本P01提案的统一主题是调查女性生育力的基石之一，排卵。通过这个P01项目，我们将解决与卵泡破裂和随后的排卵后卵泡早期变化相关的机制的关键问题。这将通过实验和技术上的科学整合来实现，涉及5名研究人员的4个独立项目将利用女性，猕猴和啮齿动物的卵巢组织。项目1（咖喱/Brannstrom）将利用一种极其新颖的模型，在该模型中，在排卵期收集人卵泡，以检查细胞外基质金属蛋白酶诱导剂（EMMPRIN）表达的变化。项目#2（Duffy）将利用Duffy博士在猕猴方面的丰富经验，研究PGE2在非人灵长类动物排卵期卵泡血管生成中的作用。项目#3（Ko）将研究孕酮调节排卵前卵巢白细胞浸润的机制。项目#4（Jo）将阐明CIPAR 1在调节LH介导的孕酮产生诱导中的细胞作用。这些项目之间的翻译相互作用很明显，因为来自女性（项目1）和猕猴（项目2）的组织可外推至啮齿动物模型（项目1、3、4）。一个行政核心为研究团队提供支持，监督该计划的整体运作，并协调不同项目中妇女、猕猴和啮齿动物的共享组织。还将支持一个试点项目，以开辟更多的研究合作和专门知识渠道。这一建议的意义在于其真正独特的翻译潜力，以进一步我们对人类排卵和早期黄体形成至关重要的途径的理解。没有比使用hCG后在规定时间收集的人类卵泡更强大的翻译潜力，以真正理解排卵和黄体化的机制。在人类和猕猴中进行的拟议研究将在促进我们对排卵相关不孕症的理解和治疗方面取得重大进展，并提供操纵人类排卵过程的治疗方式，从而为人类健康提供重要的相关性。

DESCRIPTION (provided by applicant): The unifying theme of this P01 proposal is to investigate one of the cornerstones of female fertility, ovulation. Through this P01 project, we will address key questions of the mechanisms associated with follicular rupture and the subsequent early changes in the postovulatory follicle. This will be accomplished through the scientific integration, both experimentally and technically, of 4 separate projects involving 5 investigators that will utilize ovarian tissues from women, macaques, and rodents. Project 1 (Curry/Brannstrom) will make use of an extremely novel model where human follicles are collected across the periovulatory period to examine the changes in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN). Project #2 (Duffy) will take advantage of Dr. Duffy's extensive experience with macaques to investigate the role of PGE2 in angiogenesis of the nonhuman primate periovulatory follicle. Project #3 (Ko) will study the mechanisms by which progesterone regulates leukocyte infiltration in the preovulatory ovary. Project #4 (Jo) will elucidate the cellular action of CIPAR1 in regulating the LH mediated induction of progesterone production. Translational interactions across the projects are readily evident as tissues from women (Project #1) and macaques (Project #2) will be available to extrapolate to rodent models (Projects 1, 3, 4). An Administrative core provides support for the research teams by overseeing the overall functioning of the program as well as coordinating shared tissues from women, macaques and rodents across the different projects. A pilot project will also be supported to open additional avenues of research collaboration and expertise. The significance of this proposal lies in its truly unique translational potential to further our understanding of the pathways that are critical for ovulation and early luteal formation in the human. There can be no stronger translational potential than to use human follicles collected at defined times after hCG to truly comprehend the mechanisms of ovulation and luteinization. The proposed studies in both the human and macaque will make significant strides towards advancing our understanding and treatment of ovulatory associated infertility as well as providing therapeutic modalities to manipulate the ovulatory process in the human thereby providing an important relevance to human health.