Human Endometrial Exosomes Contain Hormone-Specific Cargo Modulating Trophoblast Adhesive Capacity: Insights into Endometrial-Embryo Interactions
journal contributionposted on 2021-08-12, 06:32 authored by David GreeningDavid Greening, HPT Nguyen, K Elgass, Richard SimpsonRichard Simpson, LA Salamonsen
Embryo implantation into receptive endometrium requires synergistic endometrial-blastocyst interactions within the uterine cavity and is essential for establishing pregnancy. We demonstrate that exosomes (40-150 nm nanovesicles) released from endometrial epithelial cells are an important component of these interactions. We defined the proteome of purified endometrial epithelial-derived exosomes (Exos) influenced by menstrual cycle hormones estrogen (E; proliferative phase) and estrogen plus progesterone (EP; receptive phase) and examined their potential to modify trophoblast function. E-/EP-Exos were uniquely enriched with 254 and 126 proteins, respectively, with 35% newly identified proteins not previously reported in exosome databases. Importantly, EP-Exos protein cargo was related to fundamental changes in implantation: Adhesion, migration, invasion, and extracellular matrix remodeling. These findings from hormonally treated ECC1 endometrial cancer cells were validated in human primary uterine epithelial cell-derived exosomes. Functionally, exosomes were internalized by human trophoblast cells and enhanced their adhesive capacity, a response mediated partially through active focal adhesion kinase (FAK) signaling. Thus, exosomes contribute to the endometrialembryo interactions within the human uterine microenvironment essential for successful implantation.
This work was supported by NHMRC project grant no. 1057741 (L.A.S., R.J.S.) and the Victorian Governments Operational Infrastructure funding. L.A.S. was supported by NHMRC Fellowship no. 1002028.
JournalBiology of Reproduction
Pagination15p. (p. 1-15)
PublisherSociety for the Study of Reproduction
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Science & TechnologyLife Sciences & BiomedicineReproductive Biologyembryo implantationendometriumestrogenexosomesmicroenvironmentpregnancyprogesteroneproteomicstrophoblastCOMPLEMENT REGULATORY PROTEINSHEPARAN-SULFATE PROTEOGLYCANDENSITY-GRADIENT SEPARATIONPROTEOMIC ANALYSISEXTRACELLULAR-MATRIXCELL-LINEUTERINE RECEPTIVITYMASS-SPECTROMETRYMEDIATED ADHESIONSECRETORY PHASESEndometriumTrophoblastsHumansMaternal-Fetal RelationsEmbryo ImplantationPregnancyFemaleEmbryo, MammalianExosomesObstetrics & Reproductive Medicine