Ovarian Follicle Selection Mediated by Release from Inhibitory Map Kinase Signaling

抑制图谱激酶信号释放介导的卵巢卵泡选择

• 批准号: 0445949
• 负责人: Alan Johnson
• 金额: $ 47万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0445949&HistoricalAwards=false
• 关键词: Ovarian; Follicle; Selection; Mediated; Release

In reproductively active vertebrate females that ovulate a limited number of eggs each ovulatory cycle, it is the rate-limiting process of ovarian follicle selection that ultimately determines the number of competent follicles eventually capable of being fertilized. Vertebrate follicle selection currently represents an incompletely defined process by which an undifferentiated follicle is activated to undergo final differentiation in preparation for ovulation, whereas the likely fate of those follicles not selected is follicle death. In the hen ovary, the ovulation of a single follicle per day requires an existing preovulatory hierarchy which normally consists of a limited number of fully differentiated follicles. This follicle hierarchy is maintained by the daily 'selection' of a single follicle from a small group of undifferentiated (prehierarchal) follicles measuring 6 to 8 mm in diameter. The novel hypothesis of the research proposed is that the selection of a single, prehierarchal follicle per day into the preovulatory hierarchy is first dependent upon the release of the follicle granulosa layer from inhibitory signaling, and subsequently dependent upon an increased sensitivity to Follicle-Stimulating Hormone. A central hypothesis tested herein is that the release from inhibitory Mitogen Activated Protein Kinase signaling is prerequisite for follicle selection in the avian ovary. Furthermore, it is proposed that such MAPK signaling is promoted by the local production of one or more members of the epidermal growth factor (EGF) family of peptides. The present project describes experiments using the hen ovary model system to study endocrine, novel paracrine and autocrine factors, together with their associated membrane receptors, that tightly regulate follicle selection and subsequent differentiation. Collectively, results from the study will determine critical cellular and molecular processes that define follicle selection (and by implication reproductive potential) in a vertebrate species. Interpretations of these data are predicted to pertain to all groups within the Sauropsid lineage (e.g., oviparous reptiles, crocodiles and birds) in which the establishment of an ovarian follicle hierarchy is prerequisite for egg laying. The PI has established a record of providing teaching and research training to graduate and undergraduate students of diverse backgrounds, and is committed to the professional development of female students. The PI is an ongoing participant in the Department's REU Summer Fellows Program that serves under-represented populations, and he routinely incorporates his related research expertise into his academic lecture and laboratory curricula.

在每个排卵周期排卵的生殖活性脊椎动物女性中，这是卵巢卵泡选择的限制限制过程，最终决定了最终能够受精的胜任卵泡的数量。脊椎动物卵泡的选择当前代表了一个未完全定义的过程，通过该过程，未分化的卵泡被激活以进行排卵准备最终分化，而未选择的卵泡的可能命运是卵泡死亡。在卵巢中，每天的单个卵泡的排卵需要现有的排卵前层次结构，通常由有限数量的完全分化的卵泡组成。该卵泡层次结构是通过每天从直径为6至8 mm的一小部分未分化的（前结构）卵泡中“选择”单个卵泡的“选择”。提出的研究的新假设是，首先，每天选择一个单一的，临界前的卵泡进入抑制性信号传导中卵泡颗粒层的释放，并随后取决于对卵泡刺激激素的敏感性的增加。本文检验的中心假设是，抑制性有丝分裂激活的蛋白激酶信号的释放是禽卵卵巢中卵泡选择的先决条件。此外，有人提出，这种MAPK信号是通过局部生产表皮生长因子（EGF）家族的局部产生来促进的。本项目描述了使用HEN卵巢模型系统研究内分泌，新型旁分泌和自分泌因子以及其相关膜受体的实验，从而严格调节卵泡的选择以及随后的分化。总的来说，该研究的结果将确定脊椎动物物种中定义卵泡选择（并暗示生殖潜力）的关键细胞和分子过程。预测这些数据的解释与索罗普斯谱系中的所有群体有关（例如卵形爬行动物，鳄鱼和鸟类），其中建立卵巢卵泡层次是卵产生的先决条件。 PI已建立了为不同背景的研究生和本科生提供教学和研究培训的记录，并致力于女学生的专业发展。 PI是该部门的REU Summer Fellows计划的持续参与者，该计划服务于代表性不足的人群，他经常将相关的研究专业知识纳入他的学术讲座和实验室课程中。