Self-organising human gonads generated by a Matrigel-based gradient system.
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Authors
Oliver, Elizabeth
Alves-Lopes, João Pedro
Harteveld, Femke
Mitchell, Rod T
Åkesson, Elisabet
Söder, Olle
Publication Date
2021-09-23Journal Title
BMC Biol
ISSN
1741-7007
Publisher
Springer Science and Business Media LLC
Volume
19
Issue
1
Pages
212
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Oliver, E., Alves-Lopes, J. P., Harteveld, F., Mitchell, R. T., Åkesson, E., Söder, O., & Stukenborg, J. (2021). Self-organising human gonads generated by a Matrigel-based gradient system.. BMC Biol, 19 (1), 212. https://doi.org/10.1186/s12915-021-01149-3
Abstract
BACKGROUND: Advances in three-dimensional culture technologies have led to progression in systems used to model the gonadal microenvironment in vitro. Despite demonstrating basic functionality, tissue organisation is often limited. We have previously detailed a three-dimensional culture model termed the three-layer gradient system to generate rat testicular organoids in vitro. Here we extend the model to human first-trimester embryonic gonadal tissue. RESULTS: Testicular cell suspensions reorganised into testis-like organoids with distinct seminiferous-like cords situated within an interstitial environment after 7 days. In contrast, tissue reorganisation failed to occur when mesonephros, which promotes testicular development in vivo, was included in the tissue digest. Organoids generated from dissociated female gonad cell suspensions formed loosely organised cords after 7 days. In addition to displaying testis-specific architecture, testis-like organoids demonstrated evidence of somatic cell differentiation. Within the 3-LGS, we observed the onset of AMH expression in the cytoplasm of SOX9-positive Sertoli cells within reorganised testicular cords. Leydig cell differentiation and onset of steroidogenic capacity was also revealed in the 3-LGS through the expression of key steroidogenic enzymes StAR and CYP17A1 within the interstitial compartment. While the 3-LGS generates a somatic cell environment capable of supporting germ cell survival in ovarian organoids germ cell loss was observed in testicular organoids. CONCLUSION: The 3-LGS can be used to generate organised whole gonadal organoids within 7 days. The 3-LGS brings a new opportunity to explore gonadal organogenesis and contributes to the development of more complex in vitro models in the field of developmental and regenerative medicine.
Identifiers
External DOI: https://doi.org/10.1186/s12915-021-01149-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331194
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