Human embryo implantation and early trophoblast development have remained elusive due to the inaccessibility of the early embryo. Non-human primate models recapitulate many features of human development and allow access to early postimplantation stages. Moreover, diverging implantation strategies between primate species provide an exciting opportunity to study the regulation of trophoblast invasion. We traced the pre- to postimplantation transition of the trophoblast lineage in the marmoset embryo in vivo and derived trophoblast stem cells (TSCs) from naïve marmoset pluripotent stem cells. These cells display trophoblast-specific transcriptomic and epigenetic features, long-term self-renewal, and form polarized spheroids in vitro. Human TSC conditions did not support marmoset TSC derivation and instead induced extraembryonic mesoderm-like states. Species-specific culture with MEK, TGFβ/NODAL, and HDAC inhibition preserved a trophectoderm-like identity and revealed distinct implantation behaviours across species. In our ongoing work, we aim to build species-matched implantation platforms using endometrial organoids, stromal cells, and hydrogels and to introduce vasculature by adding HUVECs. Ultimately, these platforms will transform our understanding of implantation failure, model early pregnancy loss and provide insight into the origins of congenital disorders.
