Ovarian Follicle Selection Mediated by Release from Inhibitory Map Kinase Signaling

在生殖活跃的雌性脊椎动物中，每个排卵周期排卵有限数量的卵子，这是卵泡选择的限速过程，最终决定了最终能够受精的有能力卵泡的数量。脊椎动物卵泡选择目前代表了一个不完全定义的过程，通过该过程，未分化的卵泡被激活以进行最终分化，为排卵做准备，而未被选择的卵泡的可能命运是卵泡死亡。在母鸡卵巢中，每天单个卵泡的排卵需要一个现有的排卵前等级，通常由有限数量的完全分化的卵泡组成。这种卵泡层次是通过每天从一小群直径为6至8 mm的未分化（前层次）卵泡中选择单个卵泡来维持的。该研究提出的新假设是，每天选择一个单一的前级卵泡进入排卵前层级，首先取决于卵泡颗粒层从抑制信号中的释放，随后取决于对卵泡刺激素的敏感性增加。本文测试的中心假设是从抑制性促分裂原活化蛋白激酶信号传导的释放是禽类卵巢中卵泡选择的先决条件。此外，有人提出，这种MAPK信号是由一个或多个成员的表皮生长因子（EGF）家族的肽的局部生产。本项目描述了使用母鸡卵巢模型系统来研究内分泌、新的旁分泌和自分泌因子及其相关的膜受体的实验，所述膜受体紧密地调节卵泡选择和随后的分化。总的来说，这项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。对这些数据的解释被预测为与蜥脚类谱系内的所有类群有关（例如，卵生爬行动物、鳄鱼和鸟类），其中卵泡层次的建立是产卵的先决条件。PI已经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暑期研究员计划的持续参与者，该计划为代表性不足的人群提供服务，他经常将他的相关研究专业知识纳入他的学术讲座和实验室课程。

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.