Exosome / microvesicle regulation of oocyte developmental competence

描述(申请人提供)：卵泡在内分泌和旁分泌调节机制下都经历了一个高度协调的招募和选择过程，这样在完成这个过程时，一个或多个被卵泡包裹的卵母细胞准备好受精。在这个发育窗口期，含有大量蛋白质、miRNAs和其他大分子的丰富而高度复杂的液体聚集在卵泡腔内，有效地分离并同时培养卵丘-卵母细胞-复合体(COC)。最近的研究表明，胃窦液中含有丰富的胞外小泡，包括外切小体和微泡。这些小泡是蛋白质、microRNA和其他分子的丰富来源，可以被毛囊细胞摄取，因此可能在毛囊环境中的不同区域之间传递信息。仅在有腔卵泡内存在微泡和外体(我们以下统称为毛囊小体)，强烈地表明了发育中的卵泡内的一种新的通讯机制。尽管如此，到目前为止还没有研究确定这些囊泡在卵巢生理中的任何生物学功能。因此，我们建议使用在黄体生成素高峰前后从有腔卵泡收集的卵泡体来(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)确定卵泡体在排卵前快速变化的促黄体生成素调节机制(S)。这项研究的中心假设是，卵泡体在卵母细胞的COC成熟和随后的发育能力中起着关键作用。

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.