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Exosomes and soluble secretome from hormone-treated endometrial epithelial cells direct embryo implantation
journal contributionposted on 19.03.2021, 06:31 by S Gurung, David GreeningDavid Greening, S Catt, L Salamonsen, J Evans
© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. A successful pregnancy requires a synchronous dialogue between endometrium and embryo within the endometrial milieu. The aim of this study was to assess the role in the implantation of mediators in the endometrial milieu. Total secretome (TS), soluble secretome (SS) and small extracellular vesicles (containing exosomes) were generated from hormonally primed human endometrial epithelial cell culture medium. Human trophectoderm stem cell-derived spheroids were cultured with TS, SS or exosomes (30 mg/ml) on hormonally primed epithelial cells, with exosomes significantly increasing cell adhesion and outgrowth. Furthermore, F1 mouse 2-cell embryos were cultured in groups for 48 h followed by culture with each secretome fraction (30 mg/ml) for 48 h. Blastocyst cell number and hatching were quantified. In addition, blastocysts were further cultured on a fibronectin matrix for 72 h or transferred to recipient mice (with corresponding secretomes) with embryo implantation assessed after 6 days. Exosomes significantly increased total cell number in mouse embryos and complete hatching from zona pellucida, with both exosomes and SS significantly enhancing mouse embryo outgrowth. Importantly, exosomes increased the embryo implantation rate in comparison to other secretome fractions (normalized based on treatment amount) from the endometrial epithelia. These data indicate that endometrial epithelial exosomes support embryo growth, development and implantation while the SS has selective involvement specifically on mouse embryo outgrowth. This finding provides new insights into the molecular differences of endometrial secretome components in implantation and early embryo development and may implicate endometrial exosomes in the pathophysiology of implantation failure in infertility.
National Health Medical Research Council project grant (#1139489 to L.S., D.W.G.); Jack Brockhoff Fellowship (to J.E.); Helen Amelia Hanis Fellowship (to D.W.G.); Victorian State Government Operational Infrastructure funding to the Hudson Institute.
JournalMolecular Human Reproduction
Pagination11p. (p. 510-520)
PublisherOxford University Press
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
Science & TechnologyLife Sciences & BiomedicineDevelopmental BiologyObstetrics & GynecologyReproductive Biologyhuman endometrial epithelial cellsextracellular vesiclescrude exosomesembryo implantationhuman trophectoderm spheroidsinfertilityembryo developmentembryo transfer in miceSULFATE PROTEOGLYCAN PERLECANMOUSEREPRODUCTIONEXPRESSIONBARRIERUTERUShuman endometrial epithelial cells / extracellular vesicles / crude exosomes / embryo implantation / human trophectoderm spheroids / infertility / embryo development / embryo transfer in miceObstetrics & Reproductive Medicine