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:
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