title: Human Endometrial Exosomes Contain Hormone-Specific Cargo Modulating Trophoblast Adhesive Capacity: Insights into Endometrial-Embryo Interactions.
abstract: 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 endometrial-embryo interactions within the human uterine microenvironment essential for successful implantation.
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia d.greening@latrobe.edu.au.
authors.forename: David W
authors.initials: DW
authors.lastname: Greening
authors.affiliation: Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria, Australia hong.nguyen@hudson.org.au.
authors.forename: Hong P T
authors.initials: HP
authors.lastname: Nguyen
authors.affiliation: Monash Micro Imaging, Monash University, Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria, Australia.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Elgass
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simpson
authors.affiliation: Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria, Australia.
authors.forename: Lois A
authors.initials: LA
authors.lastname: Salamonsen
mesh_terms: D010064:Embryo Implantation / Q000502:physiology; D004622:Embryo, Mammalian / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D033261:Maternal-Fetal Relations / Q000502:physiology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
keywords: embryo implantation; endometrium; estrogen; exosomes; microenvironment; pregnancy; progesterone; proteomics; trophoblast