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HB-EGF-loaded nanovesicles enhance trophectodermal spheroid attachment and invasion
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  • Qi Hui Poh,
  • alin rai,
  • Jonathon Cross,
  • David Greening
Qi Hui Poh
Baker Heart and Diabetes Institute
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alin rai
Baker Heart and Diabetes Institute
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Jonathon Cross
Baker Heart and Diabetes Institute
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David Greening
Baker Heart and Diabetes Institute

Corresponding Author:[email protected]

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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, capable of reprogramming endometrial cells towards a pro-implantation signature and phenotype. However, challenges associated with EV yield and direct loading of biomolecules limit 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 employed a rapid NV loading strategy to encapsulate potent implantation molecules such as HB-EGF (NVHBEGF). We show these loaded NVs elicit EGFR-mediated effects in recipient endometrial cells, activating kinase phosphorylation sites that modulate their activity (AKT S124/129, MAPK1 T185/Y187), and downstream signalling pathways and processes (AKT signal transduction, GTPase activity). Importantly, they enhanced target cell attachment and invasion. The phosphoproteomics and proteomics approach highlight NVHBEGF-mediated short-term signalling patterns and long-term reprogramming capabilities on endometrial cells which functionally enhance trophectodermal-endometrial interactions. This proof-of-concept study demonstrate feasibility in enhancing the potency of NVs in the context of embryo attachment and establishment.
15 Aug 2023Submitted to PROTEOMICS
24 Aug 2023Assigned to Editor
24 Aug 2023Submission Checks Completed
24 Aug 2023Review(s) Completed, Editorial Evaluation Pending
30 Aug 2023Reviewer(s) Assigned