# Engineering the Human Endometrial–Embryo Interface: Breakthroughs in 3D Uterine Models

## TL;DR

3D organoid and co-culture models are transforming the study of human endometrial and placental biology, offering new insights into implantation and reproductive diseases.

## Contribution

The paper reviews recent breakthroughs in 3D uterine models, including assembloid systems and organ-on-a-chip technologies, enabling patient-specific and hormonally responsive studies.

## Key findings

- 3D models have successfully recapitulated mid-secretory endometrium and placental villous architecture.
- These systems reveal disease mechanisms in endometriosis, adenomyosis, and endometrial cancer.
- Emerging technologies enable long-term culture and personalized modeling of reproductive processes.

## Abstract

Three-dimensional (3D) organoid and co-culture models have emerged as transformative tools for studying human endometrial function, implantation, and placental development, overcoming key limitations of animal and two-dimensional in vitro systems. This review synthesises available information of recent advances in endometrial epithelial organoids (EEOs), trophoblast organoids (TBOs), and increasingly complex co-culture platforms incorporating stromal, vascular, and trophoblast compartments to model epithelial–stromal crosstalk, decidualisation, angiogenesis, and embryo implantation. Emerging developments include assembloid systems, synthetic and semi-synthetic extracellular matrices, and microfluidic organ-on-a-chip technologies that enable long-term culture, hormonal responsiveness, and patient-specific modelling. These approaches have recapitulated key features of the mid-secretory endometrium, placental villous architecture, trophoblast differentiation, and early implantation events while revealing disease-associated dysfunctions in conditions such as endometriosis, adenomyosis, polycystic ovarian syndrome, and endometrial cancer. Despite significant progress, current models remain limited by incomplete cellular diversity, polarity constraints, and challenges in fully modelling immune and vascular interactions. Collectively, emerging 3D organoid and co-culture systems provide physiologically relevant platforms to interrogate human reproductive biology, elucidate mechanisms underlying implantation failure and placental disease, and support the development of personalised therapeutic strategies to improve reproductive outcomes.