Reconstructing Early Human Embryonic Development: From in vitro Models to Multimodal Integration

Early human embryonic development sets the trajectory for health across the life course. Any aberrations in this process are associated with a heightened burden of adverse pregnancy outcomes. Accordingly, a comprehensive understanding of early human embryogenesis, together with the development of faithful research models, is pivotal for elucidating pregnancy physiology and pathophysiology. However, as embryonic development occurs within the uterus, direct observation has been severely limited by ethical and technical constraints.

To overcome these challenges, in vitro culture (IVC) systems have emerged as powerful platforms for studying early embryonic development under controlled conditions. These systems support human embryo development to the primitive streak anlage stage (near the 14-day ethical boundary), whereas nonhuman primate models sustain growth to neurulation and early organogenesis (up to E25), thereby bridging the gap between implantation and complex organ formation. In parallel, studies of rare early-stage primate embryos obtained from clinical procedures have yielded complementary insights into these developmental processes. In this review, we summarize recent progress in early primate embryo development research, emphasize the critical role of IVC systems in elucidating developmental processes, and discuss the integration of these experimental models with spatiotranscriptomic atlases to establish a more comprehensive framework for early human embryonic development.

Primate IVC systems offer accessible platforms for high-resolution dynamic observation and perturbation, while in vivo embryos provide physiologically faithful references. Coupling these complementary approaches reconstructs the trajectory of early human development, establishing a robust framework to decipher the causes of birth defects and facilitate mechanism-guided drug screening.