Transcriptomic changes in eutopic endometrium and ectopic lesions during endometriosis progression in a mouse model

Area of Science:

• Reproductive biology
• Genomics
• Molecular pathology

Background:

• Endometriosis is a complex condition characterized by the presence of endometrial-like tissue outside the uterus.
• Understanding the molecular mechanisms underlying endometriosis progression is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the transcriptomic alterations in both ectopic lesions and eutopic endometrial tissues during the progression of endometriosis.
• To establish and validate a mouse model that accurately reflects human endometriosis transcriptomics.

Main Methods:

• Transcriptomic analysis using RNA-sequencing was performed on ectopic lesions and eutopic endometrium from a mouse model of endometriosis.
• Differential gene expression and pathway analysis were conducted comparing endometriosis and sham control groups.
• Immunohistochemistry was used to validate immune cell infiltration in ectopic lesions.

Main Results:

• The mouse model successfully recapitulated human transcriptomic changes observed in endometriosis ectopic lesions.
• Key pathways such as estrogen activity, inflammation, angiogenesis, and fibrosis were consistently upregulated in ectopic lesions.
• Subfertile mice exhibited enhanced cholesterol/glucose synthesis and stem cell pluripotency pathways in ectopic lesions.
• Immune cell infiltration (macrophages, dendritic cells, T cells, B cells) was dysregulated in ectopic lesions.
• Specific pathways like WNT and EGF were suppressed in the eutopic endometrium of subfertile mice.

Conclusions:

• The developed mouse model serves as a valuable tool for studying endometriosis, accurately reflecting human transcriptomic changes.
• This transcriptomic analysis provides insights into the pathophysiology of endometriosis, particularly during disease progression.