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Modeling Human Gonad Development in Organoids

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

BACKGROUND:

Our learning about human reproductive development is greatly hampered due to the absence of an adequate model. Animal studies cannot truthfully recapitulate human developmental processes, and studies of human fetal tissues are limited by their availability and ethical restrictions. Innovative three-dimensional (3D) organoid technology utilizing human pluripotent stem cells (hPSCs) offered a new approach to study tissue and organ development in vitro. However, a system for modeling human gonad development has not been established, thus, limiting our ability to study causes of infertility.

METHODS:

In our study we utilized the 3D hPSC organoid culture in mini-spin bioreactors. Relying on intrinsic self-organizing and differentiation capabilities of stem cells, we explored whether organoids could mimic the development of human embryonic and fetal gonad.

RESULTS:

We have developed a simple, bioreactor-based organoid system for modeling early human gonad development. Male hPSC-derived organoids follow the embryonic gonad developmental trajectory and differentiate into multipotent progenitors, which further specialize into testicular supporting and interstitial cells. We demonstrated functional activity of the generated cell types by analyzing the expression of cell type-specific markers. Furthermore, the specification of gonadal progenitors in organoid culture was accompanied by the characteristic architectural tissue organization.

CONCLUSION:

This organoid system opens the opportunity for detailed studies of human gonad and germ cell development that can advance our understanding of sex development disorders. Implementation of human gonad organoid technology could be extended to modeling causes of infertility and regenerative medicine applications.

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Acknowledgements

We are grateful to Dr. A. Leung and Dr. V. Busa, as well as Dr. J. Wang and Dr. Honghe Liu for help with qPCR equipment setup and data collection. We would like to thank Dr. B. Zirkin and Dr. J.-Y. Chung for help with ELISA equipment setup and data collection. We thank Dr. I. Rasool from WRTC and Dr. Hooper from JHU Legacy Gift Rapid Autopsy program for coordinating the acquisition of deidentified human testis samples used for this study. Additionally, we would like to acknowledge Dr. M. Matunis for critical discussion of project design. This work was funded by the American Society for Reproductive Medicine to MVP (KY Cha Award in Stem Cell Technology) and National Institute of General Medical Sciences grant to PWJ (R01GM11755).

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  1. Marina V. Pryzhkova & Philip W. Jordan

    Present address: Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA

  2. Romina Boers

    Present address: Department of Molecular Cell Biology and Immunology, Amsterdam Universitair Medische Centra, 1117 HV, Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD, 21205, USA

    Marina V. Pryzhkova, Romina Boers & Philip W. Jordan

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The mouse studies were approved by JHU IACUC (MO21H13). The use of human ESC line was approved by JHU ISCRO committee (protocol ISCRO00000643). Deidentified decedent donor testes tissues were designated as “not human subjects research” by JHU (IRB No: 00006700).

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Pryzhkova, M.V., Boers, R. & Jordan, P.W. Modeling Human Gonad Development in Organoids. Tissue Eng Regen Med 19, 1185–1206 (2022). https://doi.org/10.1007/s13770-022-00492-y

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