Modeling the human maternal-fetal interface

Stem cells and organoids enable the modeling of various aspects of human development in vitro, yet integrating them to study maternal-fetal interactions remains challenging. In this review, we explore the current in vitro models of the endometrium, placenta, and embryo and identify key challenges associated with their integration, including the establishment of morpho-functional complexity, spatiotemporal coordination, and appropriate in vivo benchmarking. We propose an interdisciplinary perspective that emphasizes a shift from “building blocks” to “building interactions.” Altogether, we provide a discussion on the challenges and prospects for advancing mechanistic understanding of intrauterine human development and the maternal-fetal interface.