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: 9325047
• 负责人: Thomas E Curry
• 金额: $ 122.46万
• 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/9325047
• 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; 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）：该P01提案的统一主题是研究女性生育能力的基石之一。通过这个P01项目，我们将解决与卵泡破裂相关的机制以及随后卵泡后卵泡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实现，这是由4个单独的项目中的，涉及5个研究人员，这些研究人员将利用女性，猕猴和啮齿动物的卵巢组织。项目1（咖喱/布兰斯特罗姆）将利用一个非常新颖的模型，在整个卵巢周期内收集人卵泡，以检查细胞外基质基质金属蛋白酶诱导酶（EMMPRIN）表达的变化。 Project＃2（Duffy）将利用Duffy博士在猕猴中的丰富经验来研究PGE2在非人类灵长类动物周围卵泡的血管生成中的作用。项目＃3（KO）将研究孕酮调节排卵前卵巢中白细胞浸润的机制。项目＃4（JO）将阐明CIPAR1在调节LH介导的孕酮产生诱导方面的细胞作用。随着女性（项目＃1）和猕猴（项目＃2）的组织（项目＃1）的组织，可以将整个项目的翻译互动显而易见，以推断到啮齿动物模型（项目1、3、4）。行政核心通过监督该计划的整体功能，并协调各个项目中女性，猕猴和啮齿动物的共享组织，从而为研究团队提供支持。还将支持一个试点项目，以开放其他研究合作和专业知识的途径。该提案的意义在于它真正独特的翻译潜力，以进一步了解人类排卵和早期黄体形成至关重要的途径。没有比使用在HCG后定义的时间收集的人卵泡真正理解排卵和黄体化机制的人的卵泡更强的潜力。对人类和猕猴的拟议研究都将在促进我们对排卵相关的不育症的理解和治疗方面取得了长足的进步，并提供了治疗方式来操纵人类的排卵过程，从而提供了与人类健康的重要相关性。