Do interactions between endometrial derived extracellular vesicles and the microbiome mediate an optimal uterine environment?

子宫内膜来源的细胞外囊泡和微生物组之间的相互作用是否介导最佳子宫环境？

• 批准号: 2881553
• 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: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2881553
• 关键词: Do; interactions; between; endometrial; derived

For successful pregnancy in humans and livestock, the endometrium (the lining of the womb) must create the right environment for the implanting embryo. This environment is created by endometrial gland secretions, which include extracellular vesicles (ECVs): membrane bound vesicles containing microRNA and proteins that are taken up by target cells to change their function. Using novel 3D ultrastructural imaging approaches, we show that ECVs form on endometrial gland microvilli. We now need to understand how the formation and composition of endometrial ECVs are regulated. The uterine environment has a unique microbiome that interacts with the endometrial cells and is thought to modulate endometrial function and receptivity, however the mechanisms are unclear. Alteration of this microbiota or presence of certain microbiota may effect fertilization and implantation, leading to poor pregnancy outcome.We therefore need to establish whether the presence of the microbiome and substances it produces can influence the endometrial production of ECVs, be it a pathological effect or a protective response.Project plan:1) To characterise endometrial ECVs including their formation, microRNA content and establish whether these change in response to microbial presence and produced substances.2) To establish whether endometrial ECVs interact with bacterial cells within the endometrial microbiome.3) To determine whether the endometrial microbiome (from tissue and fluid samples) relates to endometrial phenotypes.Endometrial gland isolation and 3D imaging approaches are established in Southampton. The teams have expertise in isolation of ECVs, mRNA and microRNA-seq and expertise in bioinformatic analyses.We routinely collect human endometrial tissue and fluid samples from a range of fertility phenotypes.The impact of this work will come from improved understanding of the physiological role of ECVs and their regulation, plus the application of these findings to improve the success of natural and assisted conception in humans and livestock breeding programs.

为了成功怀孕在人类和牲畜中，子宫内膜（子宫内壁）必须为植入胚胎创造正确的环境。该环境是由子宫内膜分泌物创建的，其中包括细胞外囊泡（ECV）：包含靶细胞占用的蛋白质和蛋白质的膜结合囊泡以改变其功能。使用新型的3D超微结构成像方法，我们表明子宫内膜腺微绒毛形成了ECV。现在，我们需要了解子宫内膜ECV的形成和组成如何调节。子宫环境具有独特的微生物组，该微生物组与子宫内膜细胞相互作用，被认为可以调节子宫内膜功能和接受能力，但是机制尚不清楚。这种菌群的改变或某些菌群的存在可能会影响施肥和植入，从而导致妊娠不良结局。因此，我们需要确定是否存在微生物组和它产生的物质是否会影响子宫内膜的产生ECV的产生，无论是病理学效应还是一种保护性反应，以促进它们的响应。 2）要确定子宫内膜微生物组中的子宫内膜ECV是否与细菌细胞相互作用。3）确定子宫内膜微生物组（来自组织和液体样品）是否与子宫内膜表型有关。在南室中建立了内膜腺体隔离和3D成像方法。团队在隔离ECV，mRNA和microRNA-Seq以及生物信息学分析方面具有专业知识，并具有从一系列生育能力表型中收集人的子宫内膜组织和液体样本，这项工作的影响将来自对ECVS及其概念的概念的改善，并改善了这些工作的概念，从而改善了这些工作的概念，并提高了这些工作的概念，从而改善了这些概念的概念，并促进了他们的概念的应用。程序。