3D map-guided modeling of functional endometrial tissue using multi-compartment assembloids

Area of Science:

• Reproductive Biology
• Biomedical Engineering
• Gynecology

Background:

• The human endometrium's dynamic remodeling makes it prone to diseases like endometriosis and endometrial cancer.
• Current in vitro and mouse models inadequately replicate human endometrial physiology and the menstrual cycle.
• Understanding endometrial molecular mechanisms is crucial for developing targeted treatments.

Purpose of the Study:

• To develop a novel 3D multi-compartment assembloid that accurately mimics human endometrial tissue architecture and function.
• To create a platform that recapitulates all three phases of the menstrual cycle.
• To enable advanced studies of endometrial biology, disease mechanisms, and reproductive health.

Main Methods:

• Constructed a 3D multi-compartment assembloid based on a 3D spatial cellular map of endometrial tissue.
• Incorporated endometrial epithelial cells within a basement membrane and stromal cells in a collagen-rich layer.
• Tuned cellular and extracellular matrix (ECM) components to mimic native tissue interactions and hormonal responses.

Main Results:

• The assembloid successfully supported controlled cell growth and organization, mimicking endometrial tissue.
• Demonstrated reciprocal regulation of cell behavior and compartment-specific hormonal responses, including stromal decidualization.
• Validated the model's ability to recapitulate dynamic, phase-resolved, and compartment-specific paracrine signaling.

Conclusions:

• The developed 3D endometrial assembloid represents a significant advancement in modeling human reproductive tissues.
• This platform offers unprecedented opportunities for studying endometrial biology, disease pathogenesis, and blastocyst implantation.
• Sets a new benchmark for organ modeling and precision diagnostics in human reproductive health.