Objective:

To investigate whether menstrual fluid can reveal changes in endometrial epithelial signatures that may aid in the detection of endometriosis.

Approach:

• Study Design: A pilot case-control study analyzing menstrual fluid from 5 patients with confirmed endometriosis and 5 healthy controls.
• Methods: Single-nucleus RNA sequencing and bulk RNA sequencing were performed on samples collected during the heaviest day of menstruation.
• Analysis: Comparison of cell-type composition, gene expression, predicted cell-cell communication, and evaluation of candidate biomarkers.

Key Findings:

• Identified over 23,000 high-quality nuclei representing various cell populations.
• Epithelial cells showed the greatest disease-associated transcriptional differences with 36 upregulated and 53 downregulated genes.
• Altered predicted communication between endometrial and immune-cell populations was observed.
• Five genes (TIMP2, AKR1C2, DMBT1, FERMT1, KCNK5) were differentially expressed in both single-nucleus and bulk analyses, with KCNK5 showing the strongest evidence as a potential biomarker.

Interpretation:

The disease signal in endometriosis is primarily driven by transcriptional changes within epithelial cells rather than shifts in cellular composition.

Limitations:

• Pilot study with only 10 participants, limiting statistical power.
• All patients had deep infiltrating endometriosis and were nulliparous.
• Variability in menstrual fluid composition between donors.
• Potential influence of anti-inflammatory drug use on immune-related findings.

Conclusion:

Larger studies are needed to validate the proposed biomarkers and assess their performance across different endometriosis phenotypes.

Sources:

• BMC Medicine