Mediating Cross-Talk: How Uterus-Derived Extracellular Vesicles Influence Early Embryo Development and Implantation

Blastocyst formation represents an essential requirement for subsequent implantation. Successful embryo implantation depends on adequate endometrial receptivity and appropriate embryo-maternal communication. Uterus-derived extracellular vesicles (EVs), as biological nanoscale particles carrying non-coding RNAs (nc-RNAs), DNAs, proteins and lipids, play a crucial role in promoting cellular interactions and regulating maternal-foetal dialogue.

This article systematically searched the PubMed database and used the following keyword combinations for literature screening : (exosome * OR 'extracellular vesicle') AND (uter OR blastocysti) AND (blastocyst OR embryo*).

The composition of uterus-derived EVs exhibits variation across different physiological periods and plays different roles. Compared with the proliferative phase, EVs during the peri-implantation period contain more molecules related to cell differentiation, cell cycle, cell migration and invasion, apoptosis and antioxidant activity. The EVs discovered from uterine fluid, primary human endometrial epithelial cells (EECs), endometrial stromal cell and so forth have been shown to be internalised by embryos and trophoblast cell. The cargoes carried by EVs, mainly miRNA and proteins, regulate embryonic development and invasion-related pathways or molecules, supporting blastocyst formation and implantation. Similarly, EVs collected from dysfunctional uterus have been proved to disrupt critical reproductive processes, impairing both embryo development and implantation potential.

This review summarises the multiple effects of uterus-derived EVs on successful embryo implantation, including the effects on pre-implantation embryo development and embryo implantation ability.