From organoids to assembloids: modeling tissue crosstalk in female reproductive biology and disease

The female reproductive tract is a multi-tissue system in which epithelial, stromal, immune, and vascular cells coordinate responses to hormonal signals. Single-tissue organoids have advanced epithelial modeling in vitro but cannot capture the inter-tissue communication underlying key reproductive processes. Assembloids, which recombine cells from distinct tissue compartments in three-dimensional space, offer a means to restore these missing interactions. This review examines reproductive assembloid research across three biology-driven contexts. In menstrual cycle modeling, organoid-based systems have recapitulated epithelial breakdown and regeneration, yet stromal, immune, and vascular integration remain incomplete. In implantation modeling, embryo-endometrial co-cultures and receptive assembloids have begun to capture maternal-fetal crosstalk, though immune and vascular dimensions are largely missing. In endometriosis and adenomyosis modeling, assembloids have started to reconstruct pathogenic microenvironments that single organoids cannot replicate. Three issues are examined in depth. The first is the gap between what current models can and cannot reveal about reproductive biology. The second is the risk that added complexity may only confirm findings already established in vivo. The third is the point at which an additional tissue component stops contributing new information. Progress in this field is likely to depend not on greater structural complexity but on questions that only multi-tissue models can address.