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Endometrial small extracellular vesicles regulate human trophectodermal cell invasion by reprogramming the
Monique Fatmous1,2, Alin Rai1,3,4,5, Qi Hui Poh1,5,6
1Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Frontiers in Cell and Developmental Biology
|January 9, 2023
Summary
Small extracellular vesicles (sEVs) from the human endometrium promote embryo implantation by enhancing trophectodermal cell invasion. These sEVs reprogram trophectoderm cells, revealing key molecular mechanisms for early pregnancy establishment.
Area of Science:
- Reproductive biology and developmental science.
- Cellular and molecular mechanisms of pregnancy establishment.
Background:
- Successful pregnancy requires complex cyclical uterine events, including endometrial receptivity for embryo implantation.
- Small extracellular vesicles (sEVs) from endometrial cells aid trophoblast invasion, but underlying molecular pathways are unclear.
Purpose of the Study:
- To investigate the molecular mechanisms by which endometrial epithelial cell-derived sEVs facilitate human trophectodermal stem cell (hTSC) invasion.
- To identify key proteins and signaling pathways modulated by sEVs that support embryo implantation.
Main Methods:
- Purification of sEVs from human endometrial epithelial cells primed with different hormone combinations.
- Assessment of sEVs' effect on hTSC invasion in vitro using Matrigel assays.
- Proteomic and phosphoproteomic analyses of hTSCs treated with sEVs, including mass spectrometry and kinase activity assays.
Main Results:
- Endometrial sEVs were internalized by hTSCs and significantly promoted their invasion.
- Proteomic analysis revealed sEVs upregulate proteins involved in focal adhesions, embryo implantation, and kinase signaling (e.g., NRP1, FBLN1, EPHB4).
- MAPK3 phosphorylation was identified as a key mediator of sEV-induced proteome reprogramming and invasion, with inhibition abrogating the invasive phenotype.
Conclusions:
- Endometrial sEVs play a critical role in regulating trophoblast invasion through proteome reprogramming.
- The study elucidates novel molecular insights into the endometrial microenvironment's role in supporting embryo implantation via sEV-mediated signaling.
- Targeting MAPK3 signaling presents a potential avenue for understanding and potentially modulating implantation processes.
