Establishment and characterization of endometrial organoids from different placental types

Understanding molecular characteristics and metabolic processes of the mammalian endometrium is crucial for advancing biological research, particularly in veterinary obstetrics and pathology. This study established and analyzed organoids from endometrial epithelial stem cells of five mammals with different placental types: cows (cotyledonary), dogs and cats (zonary), pigs (diffuse), and rats (discoid). Organoids from these five species were maintained for over 13 passages, frozen, and thawed. Pathological analysis confirmed that they retained characteristics of their original tissues. Furthermore, integrative transcriptome analysis of organoids and tissues from the five species highlighted key pathways such as PI3K-Akt signaling and extracellular matrix-receptor interaction known to be crucial in cancer research. Although genes associated with vascular smooth muscle contraction were downregulated, these organoids exhibited significant activities of genes involved in hormone metabolism. In conclusion, our study achieved stable establishment of endometrial organoids from five mammals with different placental types, offering foundational data for organoid research. In the future, these organoids are suitable models for investigating uterine physiology and diseases and for developing potential therapies. [BMB Reports 2025; 58(2): 95-103].