From the start of the project, the project focused on generating human “blastoids” from stem cells, and modeling their interaction with endometrial cells. These blastoids provided a model to study the cellular organization and molecular interactions essential for embryo implantation, a process typically challenging to observe directly in humans. We utilized advanced stem cell culture techniques to efficiently produce blastoids, containing the key cell lineages needed for implantation.
Additionally, a parallel investigation explored the effect of mTOR signaling on early development and implantation, revealing that by inhibiting mTOR activity, human blastoids could enter a reversible dormant state. Through these experiments, we identified how human manage developmental pacing, highlighting new avenues for reproductive research.
Main Results Achieved
The main accomplishments include:
Establishment of human blastoids as a research model and studying implantation: Blastoids were successfully developed from stem cells and demonstrated characteristics closely resembling natural human blastocysts. This breakthrough offers a scalable and ethical model to investigate implantation and early embryo development, laying the groundwork for future applications in fertility and contraception research.
Discovery of mTOR-mediated dormancy in human cells: Inhibiting mTOR signaling in blastoids effectively induced a state of developmental delay, reducing growth and attachment capabilities. This finding suggests that mTOR activity could be a target to regulate embryo progression, with potential applications in managing implantation timing and understanding reproductive conditions related to early embryo development.
These results not only advance our understanding of human embryo implantation but also provide practical models and pathways that can be leveraged in reproductive health treatments. The blastoid model offers researchers a platform for high-throughput testing of drugs and genetic factors that could impact implantation. Furthermore, the insights into mTOR-mediated dormancy may inform the timing of implantation in IVF treatments, potentially improving outcomes. The research has been disseminated through publications and conferences.To share these outcomes, findings have been published in leading journals, ensuring accessibility to the wider scientific community.
Key publications include:
Generating human blastoids modeling blastocyst-stage embryos and implantation
Heidar Heidari Khoei, Alok Javali, Harunobu Kagawa, Theresa Maria Sommer, Giovanni Sestini, Laurent David, Jana Slovakova, Maria Novatchkova, Yvonne Scholte op Reimer & Nicolas Rivron, Nature Protocols, volume 18, pages 1584–1620 (2023)
mTOR activity paces human blastocyst stage developmental progression
Heidar Heidari Khoei, Dhanur P. Iyer, Vera A. van der Weijden, Harunobu Kagawa, Saurabh J. Pradhan, Maria Novatchkova, Afshan McCarthy, Teresa Rayon, Claire S. Simon, Ilona Dunkel, Sissy E. Wamaitha, Kay Elder, Phil Snell, Leila Christie, Edda G. Schulz, Kathy K. Niakan, Nicolas Rivron, and Aydan Bulut-Karslioglu, Cell
