Hormonal Signals that Regulate Ovarian Diffrentiation

描述（由申请人提供）：本申请申请西北大学P01项目“调节卵巢分化的激素信号”21-25年的续期。该项目在生殖科学方面有着悠久的合作发现研究历史，在资助期间取得了许多科学突破。该项目的主要主题是研究激素或其他调节因子作用于卵巢的信号通路，以促进维持女性生育能力所必需的甾体生成和卵泡和生殖细胞的成熟。为了研究这一主题，我们提出了三个新的研究项目，这些项目代表了我们在上一个资助期的进展和我们最近的初步发现所启发的新颖和创造性的研究方向。项目1 （Kelly Mayo和Teresa Woodruff）专注于卵巢发育和调节生殖细胞巢分解形成原始卵泡初始池的事件。这些研究使用新颖的方法来研究Notch信号，激活作用和雌激素调节在卵巢卵泡形成中的作用。《计划2》(乔恩·莱文，

DESCRIPTION (provided by applicant): This proposal requests renewal for years 21-25 of the P01 program "Hormonal Signals that Regulate Ovarian Differentiation" at Northwestern University. The program has a long history of collaborative discovery-based research in the reproductive sciences that has led to numerous scientific breakthroughs over the lifetime of the grant. The major theme of the program is to investigate signaling pathways by which hormones or other regulatory factors act on the ovary to promote steroidogenesis and the maturation of follicles and germ cells necessary to sustain female fertility. To investigate this theme, 3 new research projects are proposed that represent novel and creative research directions inspired by our progress during the last grant period and by our most recent preliminary findings. Project 1 (Kelly Mayo and Teresa Woodruff) focuses on ovarian development and the events that regulate the breakdown of germ cell nests to form the initial pool of primordial follicles. These studies use novel approaches to investigate roles for Notch signaling, activin action and estrogen regulation leading to ovarian follicle formation. Project 2 (Jon Levine, Larry Jameson, Jeff Weiss) examines later stages of follicle growth, with an emphasis on estrogen signaling through non-classical ERa pathways both within the ovary and between the ovary and the hypothalamic-pituitary axis. These studies use creative approaches to dissect mechanisms of ERa signaling in both the brain and the ovary critical to reproductive function. Project 3 (Teresa Woodruff, Tom O'Halloran) explores the final stages of follicle and oocyte maturation and investigates the inorganic signaling molecule and transition metal zinc and its actions within the female germ cell. These experiments apply exciting approaches at the chemical-biology Interface to better understand the regulation of oocyte maturation. An Administrative Core and an Ovarian Histology Core provide support that facilitates the research in the 3 scientific projects. The collective strengths of this highly interactive investigative team allow for a synergism of ideas and research collaborations that will ensure that we progress well beyond the limitations of any individual project and capture the full advantages of the P01 program mechanism. Establishment of the initial follicle pool, control of follicle function and steroidogenesis, and maturation of the female germ cell are critical issues in reproductive research that define the central theme of this program. These issues are also of fundamental importance to improving the diagnosis, understanding and treatment of diseases and dysfunctions impacting fertility, and thus are of direct relevance to human health. It is our expectation that the basic research projects presented in this P01 program proposal will have considerable impact, ultimately leading to improvements in human reproductive health.