Development of a three-dimensional culture model of endometrium to study embryo-uterine interactions

Abstract

Three-dimensional (3D) culture systems provide physiologically relevant models that better replicate in vivo cell architecture and function compared to the conventional two-dimensional cultures. In reproductive biology, 3D models of endometrial cells have emerged as powerful tools to investigate uterine physiology, embryo–maternal interactions, and implantation processes. Gel-based cultures using natural extracellular matrices such as collagen or Matrigel enable endometrial epithelial and stromal cells to form gland-like or fibroblast-like structures while maintaining hormone responsiveness and secretory activity. In addition, spheroid cultures recapitulate cell polarity, paracrine signaling, and tissue remodeling, offering insights into implantation biology and endometrial pathologies such as endometriosis. Our studies have demonstrated that bovine endometrial epithelial cells embedded in Matrigel exhibit enhanced glandular gene expression and that engineered hetero-spheroids provide stable models for studying interferon-induced matrix remodeling. Furthermore, co-culture of cultured endometrial explants with rat hatched blastocyst facilitates in vitro analysis of embryo attachment and uterine receptivity. Advances in organoid and microfluidic platforms extend these models by enabling long-term culture and dynamic hormonal regulation. Collectively, 3D culture approaches bridge the gap between in vitro experimentation and in vivo physiology, offering translational applications in reproductive medicine, livestock fertility management, and drug discovery.