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HB-EGF-loaded nanovesicles enhance trophectodermal spheroid attachment and invasion

ABSTRACT: The ability of trophectodermal cells (outer layer of the embryo) to attach to the endometrial cells and subsequently invade the underlying matrix are critical stages of embryo implantation during successful pregnancy establishment. Extracellular vesicles (EVs) have been implicated in embryo-maternal crosstalk, that reprogram endometrial cells towards a pro-implantation signature and phenotype. However, challenges associated with EV yield and direct loading of biomolecules limits their therapeutic potential. We have previously established generation of cell-derived nanovesicles (NVs) from human trophectodermal cells (hTSCs) and their capacity to reprogram endometrial cells to enhance adhesion and blastocyst outgrowth. Here, we developed a rapid NV loading strategy to encapsulate potent implantation molecules such as HB-EGF (NVHBEGF). We show these loaded NVs upon uptake to low-receptive endometrial HEC1A cells elicit EGFR-downstream pathways and enhance target cell attachment and invasion in an EGF-signalling dependent manner. This phosphoproteomics and proteomics approach reveals that NVHBEGF regulate short-term signalling (e.g., ERBB/EGFR signalling) and long-term reprogramming capabilities on endometrial cells, and demonstrate their functional regulation on trophectodermal-endometrial interactions and trophectodermal invasion. This proof-of-concept study demonstrate feasibility in enhancing the potency of NVs in the context of embryo attachment and establishment.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: David Greening

PROVIDER: MSV000092562 | MassIVE | Mon Jul 31 18:23:00 BST 2023

REPOSITORIES: MassIVE

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