Engineering the human endometrium at the intersection of development and reproduction.

Abstract

The human endometrium plays a central role in embryo implantation, pregnancy, and reproductive and systemic health, making it of great biological and clinical interest. Animal models of the endometrium often fail to mimic many intrinsic characteristics at the base of human physiology and pathology. Although two-dimensional cell-culture systems have yielded foundational insights, recent advances in three-dimensional modelling techniques have unlocked long-term culture of hormone-responsive, multicellular systems that more closely reproduce endometrial physiology. Here we trace the evolution of endometrial modelling technologies from early, reductionist approaches to next-generation organoids and multi-lineage assembloids. We discuss how these systems offer opportunities for integrative studies of tissue remodelling, reproductive disorders and maternal-embryo communication, and we highlight the remaining challenges in the field. We outline emerging frontiers at the intersection of developmental biology, bioengineering and personalized medicine, where endometrial models are advancing our understanding of human reproduction and its broader implications for women's health.