Spheroids as a model for endometriotic lesions.

Area of Science:

• Reproductive biology and immunology
• 3D cell culture models
• Endometriosis pathophysiology

Background:

• Endometriotic lesion development and progression are not well understood.
• Immune cell dysfunction and inflammation are linked to endometriosis.
• Advanced 3D in vitro models are needed to study cell-environment interactions.

Purpose of the Study:

• To develop and validate endometriotic spheroids (ES) as a 3D in vitro model.
• To investigate epithelial-stromal interactions in endometriosis.
• To model peritoneal invasion associated with endometriosis lesion development.

Main Methods:

• Generated endometriotic spheroids (ES) using immortalized endometriotic epithelial cells (12Z) and stromal cells (iEc-ESC or iHUF) in a microwell system.
• Performed transcriptomic analysis to identify differentially expressed genes in ES.
• Developed a peritoneal invasion model using human peritoneal mesothelial cells and extracellular matrix.

Main Results:

• Transcriptomic analysis revealed 4,522 differentially expressed genes in ES, with significant enrichment of inflammation-related pathways.
• Gene expression patterns in ES showed high overlap with baboon endometriotic lesions.
• The invasion model demonstrated increased invasion with estradiol or pro-inflammatory macrophages and suppression by progestin.

Conclusions:

• Endometriotic spheroids (ES) represent a suitable 3D in vitro model for studying endometriosis.
• ES facilitate the dissection of mechanisms underlying endometriotic lesion development.
• This model aids in understanding epithelial-stromal interactions and peritoneal invasion in endometriosis.