Ovulation and Luteal Formation in Rodents Monkeys and Women

啮齿动物、猴子和女性的排卵和黄体形成

• 批准号: 8609207
• 负责人: Thomas E Curry
• 金额: $ 124.33万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8609207
• 关键词: Address; Collaborations; Contraceptive methods; Critical Pathways; Dinoprostone; Extracellular Matrix; Female; Fertility; Health; Human; Human Chorionic Gonadotropin; Infertility; Infiltration; Leukocytes; Luteinization; Macaca; Matrix Metalloproteinases; Mediating; Methods; Modality; Modeling; Monkeys; Oocytes; Ovarian Tissue; Ovary; Ovulation; Pilot Projects; Process; Production; Progesterone; Research; Research Personnel; Research Support; Rodent; Rodent Model; Role; Rupture; Therapeutic; Time; Tissue Model; Tissues; Woman; angiogenesis; experience; nonhuman primate; novel; programs

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.

描述（由申请人提供）：本 P01 提案的统一主题是调查女性生育能力的基石之一——排卵。通过这个 P01 项目，我们将解决与卵泡破裂相关的机制以及排卵后卵泡随后的早期变化的关键问题。这将通过实验和技术上的科学整合来完成，涉及 5 名研究人员的 4 个独立项目，这些项目将利用女性、猕猴和啮齿动物的卵巢组织。项目 1（Curry/Brannstrom）将利用一种极其新颖的模型，在围排卵期间收集人类卵泡，以检查细胞外基质金属蛋白酶诱导物（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来研究 PGE2 在非人类灵长类排卵期卵泡血管生成中的作用。项目#3 (Ko) 将研究黄体酮调节排卵前卵巢白细胞浸润的机制。项目 #4 (Jo) 将阐明 CIPAR1 在调节 LH 介导的黄体酮产生诱导中的细胞作用。这些项目之间的转化相互作用是显而易见的，因为来自女性（项目 #1）和猕猴（项目 #2）的组织将可用于推断啮齿动物模型（项目 1、3、4）。行政核心通过监督该计划的整体运作以及协调不同项目中女性、猕猴和啮齿动物的共享组织，为研究团队提供支持。还将支持一个试点项目，以开辟更多的研究合作和专业知识途径。该提案的意义在于其真正独特的转化潜力，可以进一步加深我们对人类排卵和早期黄体形成的关键途径的理解。没有比使用 hCG 后规定时间收集的人类卵泡更能真正理解排卵和黄体化机制的转化潜力了。拟议的人类和猕猴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。