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高度协调的募集和选择过程，使得通过完成该过程，一个或多个卵泡封闭的卵母细胞准备用于受精。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，以有效地分离并同时培育卵丘-卵母细胞复合体（COC）。最近的研究表明，小的细胞外囊泡，其中包括外来体和微泡，是丰富的胃窦液。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内的不同区域之间传递信息。在窦状卵泡内，仅仅存在微泡和外泌体，我们在下文中统称为卵泡体，强烈表明发育中卵泡内的一种新的通讯机制。尽管如此，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，我们建议使用从LH峰前后的有腔卵泡中收集的卵泡体来（1）确定卵泡体对卵丘-卵母细胞复合体成熟和发育能力的影响，（2）确定LH调节机制介导排卵前卵泡体的快速变化。该研究的中心假设是卵泡体在卵母细胞的COC成熟和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.