Organoids as powerful models of endometrium epithelium in transcriptomic, cellular and functional mimicry

Organoids have emerged as revolutionary biomimetic systems that offer a physiologically relevant in vitro model to study the specific tissue or organ of origin. In the field of female reproductive biology, endometrial organoids have proven their high value in the exploration of intricate physiological processes of the endometrium such as hormonal differentiation (decidualization) and embryo-receptivity, as well as to understand the pathophysiology of diseases associated with endometrial deficits. Moreover, organoid-based adhesion models have emerged as appropriate in vitro platform that faithfully reproduces the receptive endometrium. These in vitro models offer new tools to explore the molecular mechanisms of the early embryo-endometrium interaction and to bypass the barrier of ethical restrictions. This review highlights recent advances in the endometrial research domain, focusing on endometrial epithelial organoid models that closely replicate the cellular, transcriptomic and functional characteristics of the native tissue. A comprehensive overview of the transcriptomic changes during the menstrual cycle is provided, as well as of the detailed comparison between the different cell populations of the endometrium and the endometrial organoid model. Here, we provide evidence that endometrial organoids mimic the native endometrial tissue and offer relevant tools to advance our understanding of endometrial (patho)biology, enabling us to gain insights into molecular pathways.