Role of Endometrial Extracellular Vesicles in Mediating Cell-to-Cell Communication in the Uterus: A Review

Abstract

There are several critical events that occur in the uterus during early pregnancy which are necessary for the establishment and maintenance of pregnancy. These events include blastocyst implantation, uterine decidualization, uterine neoangiogenesis, differentiation of trophoblast stem cells into different trophoblast cell lineages, and formation of a placenta. These processes involve several different cell types within the pregnant uterus. Communication between these cell types must be intricately coordinated for successful embryo implantation and the formation of a functional maternal–fetal interface in the placenta. Understanding how this intricate coordination transpires has been a focus of researchers in the field for many years. It has long been understood that maternal endometrial tissue plays a key role in intercellular signaling during early pregnancy, sending signals to nearby tissues in a paracrine manner. Recently, insights have been obtained into the mechanisms by which these signaling events occur. Notably, the endometrium has been shown to secrete extracellular vesicles (EVs) that contain crucial cargo (proteins, lipids, RNA, miRNA) that are taken up by recipient cells to initiate a response leading to the occurrence of critical events during implantation and placentation. In this review, we aim to summarize the role that endometrium-derived EVs play in mediating cell-to-cell communications within the pregnant uterus to orchestrate the events that must occur to establish and maintain pregnancy. We will also discuss how aberrant endometrial EV signaling may lead to pathophysiological conditions, such as endometriosis and infertility.

Extracellular Vesicles and Immunity: At the Crossroads of Cell Communication

“…Among the complex molecular networks that are established during pregnancy, extracellular vesicles are considered key elements of intercellular communications. Their molecular cargo regulates the crosstalk between the embryo and the uterine wall by initiating the processes of angiogenesis and tissue remodelling essential for early pregnancy [138]. Accumulating evidence shows a crucial traffic of extracellular vesicles (EVs) between the feto-placental unit and maternal immune cells in both regional and distal locations.…”

Understanding the Pathophysiology of Preeclampsia: Exploring the Role of Antiphospholipid Antibodies and Future Directions

“…Moreover, EVs have physiological roles in different organs and crucial pathological roles in the development of several diseases [73]. Therefore, EVs are a new powerful therapeutic option for various diseases, providing a potential therapeutic target and, as mentioned, a platform for therapeutic interventions and/or delivery [77].…”

Enrichment of Bioactive Lipids in Urinary Extracellular Vesicles and Evidence of Apoptosis in Kidneys of Hypertensive Diabetic Cathepsin B Knockout Mice after Streptozotocin Treatment

“…EVs have been shown to have beneficial roles and, in other cases, can contribute to pathophysiology [1]. These nano-sized vesicles carry various types of lipids, proteins, and nucleic acids from one cell to another to allow for intercellular communication [2,3] and intracellular signaling [4,5]. The secretion of EVs is regulated by various biological stimuli, drugs, and the post-translational modification or activation/inhibition of proteins.…”