The role of endometrial gland derived extracellular vesicles in mediating an optimal uterine environment.

子宫内膜腺衍生的细胞外囊泡在调节最佳子宫环境中的作用。

• 批准号: 2596730
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2596730
• 关键词: role; endometrial; gland; derived; extracellular

Rationale: For successful pregnancy in humans and livestock, the endometrium (the lining of the womb) must create the right environment for the implanting embryo. Endometrial gland secretions, which include extracellular vesicles, create this environment. Extracellular vesicles (ECVs) are membrane bound vesicles containing microRNA and proteins, which are taken up by target cells and change their function. Using novel 3D ultrastructural imaging approaches, we have shown that ECVs form on the tips of endometrial gland microvilli (Fig 1). This is a novel finding as ECVs had been thought to form in a very different manner. We now need to understand how the ECVs are formed in endometrial glands and determine how this can be regulated by hormonal and nutritional factors. We need to establish what microRNAs and proteins the endometrial ECVs contain, whether these relate to endometrial phenotype, and what effects these microRNAs could have on gene expression pathways in the embryo. Project plan: 1) To study the formation of ECVs in isolated human endometrial glands and establish whether this can be altered by hormonal or nutritional stimuli. 2) To characterise endometrial ECVs including their microRNA content and establish whether this changes in response to hormonal or nutritional stimuli. 3) To perform an in-silico analysis to determine the target genes of the ECV microRNAs and seek to test these predictions in an embryonic cell line. Endometrial gland isolation and 3D imaging approaches are established in Southampton. The Sussex and Southampton teams have expertise in isolation of ECVs, microRNA-seq from human and animal tissue and serum, and expertise in bioinformatic analyses. The impact of this work will come from an improved understanding of the physiological role of ECVs and their regulation and from the application of these findings to improve the success of natural and assisted conception in humans and livestock breeding programs.

基本原理：为了在人类和牲畜中成功怀孕，子宫内膜（子宫内膜）必须为植入胚胎创造合适的环境。子宫内膜腺分泌物，包括细胞外囊泡，创造了这种环境。细胞外囊泡（extracellular vesicles，ECV）是一种膜结合囊泡，含有微小RNA和蛋白质，被靶细胞摄取后改变其功能。利用新的3D超微结构成像方法，我们发现ECV形成于子宫内膜腺微绒毛的顶端（图1）。这是一个新的发现，因为ECV被认为是以非常不同的方式形成的。我们现在需要了解ECV是如何在子宫内膜腺体中形成的，并确定如何通过激素和营养因素进行调节。我们需要确定子宫内膜ECV包含哪些microRNA和蛋白质，这些microRNA和蛋白质是否与子宫内膜表型相关，以及这些microRNA对胚胎基因表达途径的影响。项目计划：1）研究离体人子宫内膜腺体中ECV的形成，并确定这是否可以通过激素或营养刺激来改变。2)检测子宫内膜ECV，包括其microRNA含量，并确定其是否响应于激素或营养刺激而发生变化。3)进行计算机分析以确定ECV microRNA的靶基因，并试图在胚胎细胞系中测试这些预测。子宫内膜腺体分离和3D成像方法在南安普顿建立。苏塞克斯和南安普顿的团队在分离ECV、从人类和动物组织和血清中分离microRNA-seq以及生物信息学分析方面具有专业知识。这项工作的影响将来自对ECV生理作用及其调节的更好理解，以及这些发现的应用，以提高人类和牲畜育种计划中自然和辅助受孕的成功率。