Endometriosis: one step closer to a diagnostic test using menstrual fluid

Endometriosis is a chronic gynecological condition in which tissue normally lining the uterus, known as the endometrium, grows outside it. It can cause severe pelvic pain, heavy menstrual bleeding, fatigue, and can also lead to infertility. It affects around one in ten women of childbearing age.

Why is endometriosis so difficult to diagnose?

Although the condition is very common, it remains difficult to detect. It is currently diagnosed based on symptoms and either MRI or ultrasound imaging, and there are no reliable biomarkers enabling simple, non-invasive detection. A biomarker is a biological signature that can be measured in a specimen such as a blood sample. Without such a tool, women have to wait four to eleven years on average for a diagnosis.

Why investigate menstrual fluid?

Peripheral blood, typically collected from a vein, has so far provided few clinically usable markers for endometriosis. However, menstrual fluid contains cells that originate directly in the endometrium. It therefore offers an extremely useful window for biological observation that can be accessed without any invasive procedures.

Camille Berthelot, head of the Comparative Functional Genomics Group at the Institut Pasteur and her team analyzed these cells at very high resolution using single-cell RNA sequencing. "With this technique, it is possible to read the activity of all genes in each cell individually and compare these profiles between women with endometriosis and those unaffected by the condition," she explains.
 

Which cells carry the signature of the disease?

Of all the different cell types analyzed, the endometrial epithelial cells lining the uterine wall exhibited the most pronounced differences. Over 400 genes in these cells function differently in affected women. These are involved in hormone response, tissue remodeling, inflammation and cell proliferation, which are all mechanisms with known links to endometriosis. In contrast, differences between the two groups' immune cells were less significant.

Camille Berthelot's team also demonstrated that interactions between endometrial cells were disrupted in patients. This dysregulation could play a role in the development of the condition.
 

Five candidate genes for a future diagnostic test

Of the hundreds of genes analyzed, five stood out as potential novel biomarkers: TIMP2, AKR1C2, DMBT1, FERMT1 and KCNK5.

Their expression profile in menstrual fluid could provide the basis for developing a non-invasive diagnostic test capable of being performed on a sample during menstruation.

Such a tool would help reduce time to diagnosis and allow patients to access treatment earlier. These findings also improve understanding of disease mechanisms and could eventually contribute to the development of more targeted treatments. However, they need to be confirmed with larger patient cohorts before any clinical application is possible.
 

Source : Single-nucleus analysis of menstrual fluid highlights gene expression differences in epithelial cells of endometriosis donors, BMC Medicine, June 30, 2026

Work on endometriosis falls under the "Origins of diseases" scientific priority of the Pasteur 2030 strategic plan aimed at investigating the mechanisms underlying non-communicable diseases and inflammation.