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.

为了人类和牲畜的成功怀孕，子宫内膜（子宫的衬里）必须为胚胎植入创造合适的环境。这种环境是由子宫内膜腺分泌物创造的，其中包括细胞外囊泡（ecv）：含有microRNA和蛋白质的膜结合囊泡，被靶细胞吸收以改变其功能。利用新颖的三维超微结构成像方法，我们发现ecv在子宫内膜腺微绒毛上形成。我们现在需要了解子宫内膜ecv的形成和组成是如何被调节的。子宫环境具有独特的微生物群，可与子宫内膜细胞相互作用，并被认为可调节子宫内膜功能和接受性，但其机制尚不清楚。这种微生物群的改变或某些微生物群的存在可能影响受精和着床，导致不良妊娠结局。因此，我们需要确定微生物组及其产生的物质的存在是否会影响ecv的子宫内膜生成，无论是病理效应还是保护性反应。项目计划：1)表征子宫内膜ecv，包括其形成、microRNA含量，并确定这些是否随微生物的存在和产生的物质而变化。2)确定子宫内膜ecv是否与子宫内膜微生物组内的细菌细胞相互作用。3)确定子宫内膜微生物组（来自组织和液体样本）是否与子宫内膜表型相关。子宫内膜腺分离和3D成像方法在南安普顿建立。该团队在分离ecv、mRNA和microRNA-seq以及生物信息学分析方面具有专业知识。我们定期收集人类子宫内膜组织和液体样本，从一系列生育表型。这项工作的影响将来自于对ecv生理作用及其调控的更好理解，以及这些发现在人类和牲畜育种计划中的应用，以提高自然受孕和辅助受孕的成功率。