Journal
BIOLOGY OF REPRODUCTION
Volume 94, Issue 2, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1095/biolreprod.115.134890
Keywords
embryo implantation; endometrium; estrogen; exosomes; microenvironment; pregnancy; progesterone; proteomics; trophoblast
Categories
Funding
- NHMRC project [1057741]
- Victorian Governments Operational Infrastructure funding
- NHMRC Fellowship [1002028]
- National Health and Medical Research Council of Australia [1057741] Funding Source: NHMRC
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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.
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