The post-implantation phase of mammalian development is crucial yet challenging to study due to ethical and technical constraints, particularly in humans. Recent revolutionary advances in extended in vitro culture systems for mammalian embryos now offer unprecedented windows into this developmental “black box”. This review synthesizes how these platforms, alongside stem cell-derived embryo models, are transforming our ability to model early human development in a dish. We detail the technological evolution from two-dimensional (2D) to three-dimensional (3D) cultures that support mouse, non-human primate, and human embryos through key stages of implantation and gastrulation, recapitulating events like lineage specification and axial patterning. Furthermore, we explore how these models serve as powerful tools for investigating the etiology of early pregnancy failure, screening for developmental toxicity of pharmaceuticals, and deciphering the molecular pathogenesis of birth defects. By bridging fundamental embryology with clinical and pharmacological applications, these innovative models herald a new era in biomedical research, holding significant promise for advancing reproductive medicine and regenerative strategies.
Liu et al. (2026) studied this question.