Female Reproductive System Assembloids in Health and Disease

In just over a decade, in vitro modeling of the female reproductive tract has advanced from planar monolayers of immortalized cells to self-organizing epithelial organoids and, most recently, to increasingly complex multicellular and multicompartment 3D models, including assembloids that combine organoids with additional organoid modules or specialized cell lineages and demonstrate post-assembly integration and self-organization. This review concentrates deliberately on organoid, assembloid, and related multicellular 3D models rather than on reproductive physiology per se. We first establish a criterion-based framework that distinguishes organoids, assembloids, co-cultures, organ-on-chip systems, and blastoids according to assembly strategy, cellular composition, and evidence of structural and functional integration, and trace the rapid consolidation of the assembloid concept from neuroscience into reproductive biology. We then survey, organ-by-organ and with a critical eye, what these models have demonstrated in the endometrium, the ovary and follicle, the fallopian tube, and the embryo-maternal interface, together with the enabling technologies (including microfluidics, vascularization strategies, biomaterials and bioprinting, and single-cell and spatial benchmarking) and the limitations that still constrain the field. We close with emerging translational opportunities in disease modeling, drug and toxicology screening, and personalized reproductive medicine, while highlighting the requirements for physiological validation, reproducibility, standardization, and appropriate ethical and regulatory oversight.