Decoding adenomyosis pathogenesis using an assembloid model

Area of Science:

• Gynecology
• Cell Biology
• Tissue Engineering

Background:

• Adenomyosis research is hindered by the lack of accurate in vitro models.
• Existing models do not fully replicate endometrial tissue dynamics throughout the menstrual cycle.

Purpose of the Study:

• To establish a novel endometrial assembloid model for studying adenomyosis.
• To investigate the cellular and molecular mechanisms underlying adenomyosis pathogenesis.

Main Methods:

• Development of a 3D endometrial assembloid model.
• Single-cell transcriptomics to analyze cellular changes.
• Analysis of stromal-epithelial signaling pathways.

Main Results:

• The assembloid model accurately mimics cycle-dependent endometrial responses and adenomyosis hallmarks.
• Ectopic epithelial cells exhibit a luminal-dominant, glandular-deficient profile during the secretory phase.
• Stromal reorganization involves loss of BMP4+ cells and gain of CRYAB+IL15+ cells, impairing BMP signaling and activating WNT signaling.
• Ectopic cells show increased immunity and angiogenesis.

Conclusions:

• The endometrial assembloid platform provides a physiologically relevant model for adenomyosis research.
• Aberrant WNT signaling is implicated in adenomyosis pathogenesis and represents a potential therapeutic target.
• This model offers new avenues for developing mechanism-driven treatment strategies for adenomyosis.