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Human Endometrial Exosomes Contain Hormone-Specific Cargo Modulating Trophoblast Adhesive Capacity: Insights into Endometrial-Embryo Interactions

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posted on 12.08.2021, 06:32 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.

Funding

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.

History

Publication Date

01/01/2016

Journal

Biology of Reproduction

Volume

94

Issue

2

Article Number

38

Pagination

15p. (p. 1-15)

Publisher

Society for the Study of Reproduction

ISSN

0006-3363

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