Ovarian Follicle Selection Mediated by Release from Inhibitory Map Kinase Signaling

在每个排卵周期排卵数量有限的生殖活跃的脊椎动物雌性中，卵巢卵泡选择的速率限制过程最终决定了最终能够受精的合格卵泡的数量。脊椎动物卵泡选择目前代表了一个不完全定义的过程，通过这个过程，未分化的卵泡被激活，进行最终分化，为排卵做准备，而那些未被选择的卵泡可能的命运是卵泡死亡。在母鸡卵巢中，每天一个卵泡的排卵需要一个现有的排卵前等级，该等级通常由有限数量的完全分化的卵泡组成。这种卵泡等级是通过每天从一小群直径为6至8毫米的未分化（分级前）卵泡中“选择”一个卵泡来维持的。该研究提出的新假设是，每天选择一个卵泡进入排卵期前的卵泡首先取决于卵泡颗粒层从抑制信号中释放出来，随后取决于对促卵泡激素的敏感性增加。本文检验的一个中心假设是，抑制丝裂原活化蛋白激酶信号的释放是鸟类卵巢卵泡选择的先决条件。此外，研究人员提出，这种MAPK信号是由表皮生长因子（EGF）家族肽的一个或多个成员的局部产生促进的。本项目描述了利用母鸡卵巢模型系统研究内分泌、新型旁分泌和自分泌因子及其相关的膜受体，这些因子密切调节卵泡选择和随后的分化。总的来说，研究结果将确定脊椎动物卵泡选择（以及生殖潜力）的关键细胞和分子过程。据预测，对这些数据的解释适用于蜥脚类动物谱系中的所有类群（如卵生爬行动物、鳄鱼和鸟类），其中卵泡等级的建立是产卵的先决条件。学院为不同背景的研究生和本科生提供教学和研究培训，并致力于女学生的专业发展。PI是该部门REU夏季研究员计划的持续参与者，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.