Trophoblast derived extracellular vesicles trigger secondary vesicle release from endometrial epithelial cells.
7 affiliations
- 1Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, 51006, Estonia.
- 2Department of Animal Science, Faculty of Agriculture, University of Peradeniya, Peradeniya, 20400, Sri Lanka.
- 3Institute of Chemistry, University of Tartu, Tartu, 50411, Estonia.
- 4Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia.
- 5Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, 51006, Estonia. [email protected].
- 6Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, 50411, Estonia. [email protected].
- 7Division of Clinical Medicine, School of Medicine & Population Health, Medical School, University of Sheffield, Sheffield, S10 2SF, UK. [email protected].
Abstract
Extracellular vesicles (EVs) are emerging mediators of cellular communication, carrying bioactive molecules that can alter the function of recipient cells. Yet, how these signals are recognized and interpreted by recipient cells remains unclear. For communication to be effective, signals must reach the right cells at the right time, suggesting that EVs likely target specific cells, an aspect often overlooked in mechanistic studies.In this study, we used an in vitro embryo implantation model consisting of JAr (trophoblast) and RL95-2 (endometrial) cells to explore targeted communication in a physiologically relevant context. Our previous findings showed that JAr-derived EVs specifically induce rapid secretion of milk fat globule epidermal growth factor-8 (MFGE8) from RL95-2 cells. Using MFGE8 as a functional readout, we further investigated the underlying mechanisms of EV mediated targeted cell communication.We found that RL95-2 responses to JAr EVs depend on clathrin-mediated endocytosis and endosomal acidification. Moreover, Rab27a-dependent secondary vesicle release contributed to increased MFGE8 secretion in endometrial cells. Importantly, optimal EV activity required precise pairing between EVs and recipient cells, indicating that EV-triggered vesicle release is not merely a recycling process. Finally, recipient cell stress disrupted vesicle release and impaired responses to EV signals. By combining this in vitro model with MFGE8 as a rapid functional readout, we highlight a natural mechanism of targeted EV communication.
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BibTeX
@article{muhandiram2026trophoblast,
title = {{Trophoblast derived extracellular vesicles trigger secondary vesicle release from endometrial epithelial cells.}},
author = {Subhashini Muhandiram and Seyed Omid Reza Mousavi and Suranga Kodithuwakku and Kasun Godakumara and Sergei Kopanchuk and Ago Rinken and Getnet Midekessa and Alireza Fazeli},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03096-4},
url = {https://europepmc.org/article/MED/42897637},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Trophoblast derived extracellular vesicles trigger secondary vesicle release from endometrial epithelial cells.
AU - Subhashini Muhandiram
AU - Seyed Omid Reza Mousavi
AU - Suranga Kodithuwakku
AU - Kasun Godakumara
AU - Sergei Kopanchuk
AU - Ago Rinken
AU - Getnet Midekessa
AU - Alireza Fazeli
PY - 2026
DA - 2026/07/01
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03096-4
UR - https://europepmc.org/article/MED/42897637
AB - Extracellular vesicles (EVs) are emerging mediators of cellular communication, carrying bioactive molecules that can alter the function of recipient cells. Yet, how these signals are recognized and interpreted by recipient cells remains unclear. For communication to be effective, signals must reach the right cells at the right time, suggesting that EVs likely target specific cells, an aspect often overlooked in mechanistic studies.In this study, we used an in vitro embryo implantation model consisting of JAr (trophoblast) and RL95-2 (endometrial) cells to explore targeted communication in a physiologically relevant context. Our previous findings showed that JAr-derived EVs specifically induce rapid secretion of milk fat globule epidermal growth factor-8 (MFGE8) from RL95-2 cells. Using MFGE8 as a functional readout, we further investigated the underlying mechanisms of EV mediated targeted cell communication.We found that RL95-2 responses to JAr EVs depend on clathrin-mediated endocytosis and endosomal acidification. Moreover, Rab27a-dependent secondary vesicle release contributed to increased MFGE8 secretion in endometrial cells. Importantly, optimal EV activity required precise pairing between EVs and recipient cells, indicating that EV-triggered vesicle release is not merely a recycling process. Finally, recipient cell stress disrupted vesicle release and impaired responses to EV signals. By combining this in vitro model with MFGE8 as a rapid functional readout, we highlight a natural mechanism of targeted EV communication.
SN - 1478-811X
ER -