Exosome / microvesicle regulation of oocyte developmental competence

描述（由申请人提供）：卵巢卵泡在内分泌和旁分泌调节机制下经历了一个高度协调的招募和选择过程，这样在这个过程完成后，一个或多个卵泡封闭的卵母细胞准备受精。在这个发育窗口期，含有大量蛋白质、mirna和其他大分子的丰富且高度复杂的液体在卵泡腔内积累，有效地分离并同时培养卵母细胞复合物（COC）。最近的研究表明，小的细胞外囊泡，包括外泌体和微囊泡，在胃窦液中丰富。这些囊泡是蛋白质、microrna和其他分子的丰富来源，这些分子可以被滤泡细胞吸收，因此可以在滤泡环境的不同区域之间传递信息。微囊泡和外泌体（下文统称为滤泡体）在卵泡腔内的存在，有力地表明在发育中的卵泡内存在一种新的通讯机制。尽管如此，目前还没有研究确定这些囊泡在卵巢生理学中的任何生物学功能。因此，我们建议使用在黄体生成素激增前后收集的卵泡体来(1)确定卵泡体对卵丘-卵母细胞复合物成熟和发育能力的影响；(2)确定排卵前介导卵泡体快速变化的LH调节机制。该研究的中心假设是卵泡小体在COC成熟和卵母细胞随后的发育能力中起关键作用。

DESCRIPTION (provided by applicant): Ovarian follicles undergo a highly orchestrated recruitment and selection process under both endocrine and paracrine regulatory mechanisms, such that by the completion of the process, one or more follicle-enclosed oocytes are prepared for fertilization. During this developmental window, a rich and highly complex fluid containing numerous proteins, miRNAs, and other macromolecules accumulates within the follicular antrum to effectively isolate and simultaneously nurture the cumulus-oocyte-complex (COC). Recent studies have shown that small extracellular vesicles, which include exosomes and microvesicles, are abundant within antral fluid. These vesicles are a rich source of proteins, microRNAs and other molecules that can be taken-up by follicular cells and thus may transmit messages between varying regions within follicular environment. The mere presence of microvesicles and exosomes, which we hereafter refer to collectively as folliculosomes, within the antral follicle, strongly suggests a novel mechanism of communication within the developing follicle. Despite this, no studies have as yet identified any biological function of these vesiclesin ovarian physiology. Therefore, we propose to use folliculosomes collected from antral follicles before and after the LH surge to (1) determine the effects of folliculosomes on maturation and developmental competence of cumulus-oocyte complexes and (2) identify the LH-regulatory mechanism(s) that mediate the rapid changes in folliculosomes prior to ovulation. The central hypothesis of the proposed research is that folliculosomes play critical roles in COC maturation and subsequent developmental competence of the oocyte.