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10.3390/cells9051121
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Article

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

by
Alice Luddi
1,†,
Valentina Pavone
1,†,
Bianca Semplici
1,
Laura Governini
1,
Mattia Criscuoli
2,
Eugenio Paccagnini
3,
Mariangela Gentile
3,
Giuseppe Morgante
1,
Vincenzo De Leo
1,
Giuseppe Belmonte
1,
Natasa Zarovni
2 and
Paola Piomboni
1,*
1
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
2
Exosomics, SpA, 53100 Siena, Italy
3
Department of Life Sciences, University of Siena, 53100 Siena, Italy
*
Author to whom correspondence should be addressed.
†
The authors consider that the first two authors should be regarded as joint first authors.
Cells 2020, 9(5), 1121; https://doi.org/10.3390/cells9051121
Submission received: 1 April 2020 / Revised: 22 April 2020 / Accepted: 30 April 2020 / Published: 30 April 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms Underlying Embryo Implantation)
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Abstract

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.
Keywords: 3D-cell culture; human endometrium; implantation; Glycodelin A; endometriosis 3D-cell culture; human endometrium; implantation; Glycodelin A; endometriosis

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MDPI and ACS Style

Luddi, A.; Pavone, V.; Semplici, B.; Governini, L.; Criscuoli, M.; Paccagnini, E.; Gentile, M.; Morgante, G.; De Leo, V.; Belmonte, G.; et al. Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site. Cells 2020, 9, 1121. https://doi.org/10.3390/cells9051121

AMA Style

Luddi A, Pavone V, Semplici B, Governini L, Criscuoli M, Paccagnini E, Gentile M, Morgante G, De Leo V, Belmonte G, et al. Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site. Cells. 2020; 9(5):1121. https://doi.org/10.3390/cells9051121

Chicago/Turabian Style

Luddi, Alice, Valentina Pavone, Bianca Semplici, Laura Governini, Mattia Criscuoli, Eugenio Paccagnini, Mariangela Gentile, Giuseppe Morgante, Vincenzo De Leo, Giuseppe Belmonte, and et al. 2020. "Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site" Cells 9, no. 5: 1121. https://doi.org/10.3390/cells9051121

APA Style

Luddi, A., Pavone, V., Semplici, B., Governini, L., Criscuoli, M., Paccagnini, E., Gentile, M., Morgante, G., De Leo, V., Belmonte, G., Zarovni, N., & Piomboni, P. (2020). Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site. Cells, 9(5), 1121. https://doi.org/10.3390/cells9051121

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