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Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site

Embryo implantation has been defined as the “black box” of human reproduction. Most of the knowledge on mechanisms underlining this process derives from animal models, but they cannot always be translated to humans. Therefore, the development of an in vitro/ex vivo model recapitulating as closely an...

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Autores principales: Luddi, Alice, Pavone, Valentina, Semplici, Bianca, Governini, Laura, Criscuoli, Mattia, Paccagnini, Eugenio, Gentile, Mariangela, Morgante, Giuseppe, De Leo, Vincenzo, Belmonte, Giuseppe, Zarovni, Natasa, Piomboni, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291023/
https://www.ncbi.nlm.nih.gov/pubmed/32366044
http://dx.doi.org/10.3390/cells9051121
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author Luddi, Alice
Pavone, Valentina
Semplici, Bianca
Governini, Laura
Criscuoli, Mattia
Paccagnini, Eugenio
Gentile, Mariangela
Morgante, Giuseppe
De Leo, Vincenzo
Belmonte, Giuseppe
Zarovni, Natasa
Piomboni, Paola
author_facet Luddi, Alice
Pavone, Valentina
Semplici, Bianca
Governini, Laura
Criscuoli, Mattia
Paccagnini, Eugenio
Gentile, Mariangela
Morgante, Giuseppe
De Leo, Vincenzo
Belmonte, Giuseppe
Zarovni, Natasa
Piomboni, Paola
author_sort Luddi, Alice
collection PubMed
description Embryo implantation has been defined as the “black box” of human reproduction. Most of the knowledge on mechanisms underlining this process derives from animal models, but they cannot always be translated to humans. Therefore, the development of an in vitro/ex vivo model recapitulating as closely and precisely as possible the fundamental functional features of the human endometrial tissue is very much desirable. Here, we have validated endometrial organoids as a suitable 3D-model to studying epithelial endometrial interface for embryo implantation. Transmission and scanning electron microscopy analyses showed that organoids preserve the glandular organization and cell ultrastructural characteristics. They also retain the responsiveness to hormonal treatment specific to the corresponding phase of the menstrual cycle, mimicking the in vivo glandular-like aspect and functions. Noteworthy, organoids mirroring the early secretive phase show the development of pinopodes, large cytoplasmic apical protrusions of the epithelial cells, traditionally considered as reliable key features of the implantation window. Moreover, organoids express glycodelin A (GdA), a cycle-dependent marker of the endometrial receptivity, with its quantitative and qualitative features accounting well for the profile detected in the endometrium in vivo. Accordingly, organoids deriving from the eutopic endometrium of women with endometriosis show a GdA glycosylation pattern significantly different from healthy organoids, confirming our prior data on endometrial tissues. The present results strongly support the idea that organoids may closely recapitulate the molecular and functional characteristics of their cells/tissue of origin.
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spelling pubmed-72910232020-06-17 Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site Luddi, Alice Pavone, Valentina Semplici, Bianca Governini, Laura Criscuoli, Mattia Paccagnini, Eugenio Gentile, Mariangela Morgante, Giuseppe De Leo, Vincenzo Belmonte, Giuseppe Zarovni, Natasa Piomboni, Paola Cells Article Embryo implantation has been defined as the “black box” of human reproduction. Most of the knowledge on mechanisms underlining this process derives from animal models, but they cannot always be translated to humans. Therefore, the development of an in vitro/ex vivo model recapitulating as closely and precisely as possible the fundamental functional features of the human endometrial tissue is very much desirable. Here, we have validated endometrial organoids as a suitable 3D-model to studying epithelial endometrial interface for embryo implantation. Transmission and scanning electron microscopy analyses showed that organoids preserve the glandular organization and cell ultrastructural characteristics. They also retain the responsiveness to hormonal treatment specific to the corresponding phase of the menstrual cycle, mimicking the in vivo glandular-like aspect and functions. Noteworthy, organoids mirroring the early secretive phase show the development of pinopodes, large cytoplasmic apical protrusions of the epithelial cells, traditionally considered as reliable key features of the implantation window. Moreover, organoids express glycodelin A (GdA), a cycle-dependent marker of the endometrial receptivity, with its quantitative and qualitative features accounting well for the profile detected in the endometrium in vivo. Accordingly, organoids deriving from the eutopic endometrium of women with endometriosis show a GdA glycosylation pattern significantly different from healthy organoids, confirming our prior data on endometrial tissues. The present results strongly support the idea that organoids may closely recapitulate the molecular and functional characteristics of their cells/tissue of origin. MDPI 2020-04-30 /pmc/articles/PMC7291023/ /pubmed/32366044 http://dx.doi.org/10.3390/cells9051121 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luddi, Alice
Pavone, Valentina
Semplici, Bianca
Governini, Laura
Criscuoli, Mattia
Paccagnini, Eugenio
Gentile, Mariangela
Morgante, Giuseppe
De Leo, Vincenzo
Belmonte, Giuseppe
Zarovni, Natasa
Piomboni, Paola
Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site
title Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site
title_full Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site
title_fullStr Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site
title_full_unstemmed Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site
title_short Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site
title_sort organoids of human endometrium: a powerful in vitro model for the endometrium-embryo cross-talk at the implantation site
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291023/
https://www.ncbi.nlm.nih.gov/pubmed/32366044
http://dx.doi.org/10.3390/cells9051121
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