Periodic Reporting for period 1 - MultiMENDo (Menstrual blood multiomics analysis to better diagnose, understand and treat endometriosis)
Reporting period: 2023-05-01 to 2025-10-31
The MultiMENDo project aims at finding diagnostic biomarkers and prognostic biomarker candidates, as well as investigating new therapeutic approaches for endometriosis using menstrual fluid, an easily accessible yet overlooked biological fluid.
Endometriosis is a common gynecological disorder affecting 6-10% of women of childbearing age. It is associated with pelvic pain and infertility. It leads to a reduced quality of life and is an economic burden. It is defined by the presence of endometrial tissue (the lining mucosa of the uterus), forming endometriotic lesion, outside the uterus. Endometriotic lesion form from retrograde menstruation (menstrual fluid reflux through the fallopian tubes) but the precise pathogenesis remains unclear. There are no noninvasive biomarkers currently used in clinical care but they are essential to improve the diagnosis delay, currently estimated at 8 years. There is no specific treatment and pharmacological options are contraceptive. Within this project, we will use menstrual fluid as a relevant biological fluid for endometriosis. We will compare the gene expression profile of each of the cells contained in the menstrual fluid of women affected or not by endometriosis. We will look at the molecules that can be found outsides of these cells in the menstrual fluid. With thisinformation, we will used computational tools to identify candidate diagnostic biomarkers that differentiate endometriosis affected women from healthy controls. We will then validate the usefullness of these biomarkers in additional menstrual fluid samples from a total of 250 women. In parallel, we will generate 3D cellular models derived from the menstrual fluid cells of women with or without endometriosis. These 3D models will be cultivated in vitro with immune cells to better understand the interaction between the endometrial and immune cells. This will allow us to design and test new immunomodulatory treatments. Finally, we will also look for prognostic/predictive candidate biomarkers in two context : in response to surgery and in vitro fertilization (IVF). A prognostic biomarker could allow a better follow up of the disease after surgery (to monitor that it is not coming back for example). To identify such potential biomarkers, we will compare the gene expression profile in menstrual fluid cells obtained before and after the endometriosis surgery. A predictive biomarker for IVF may allow to predict the sucess of such procedure and potentially have some hypothesis for a lack of success. To identify such potential biomarkers, we will assess the gene expression profile in menstrual fluid cells obtained before an IVF procedure and compare the samples from women with a positive versus a negative pregnancy test following the IVF.
Diagnostic and prognostic/predictive biomarkers are essential to assess disease establishment, evolution and to choose the most appropriate treatment. This project will enhance our understanding of endometriosis pathophysiology as well as allow the study of menstrual blood, a relevant biological fluid for gynecology and reproductive disorders.
Endometriosis is a common gynecological disorder affecting 6-10% of women of childbearing age. It is associated with pelvic pain and infertility. It leads to a reduced quality of life and is an economic burden. It is defined by the presence of endometrial tissue (the lining mucosa of the uterus), forming endometriotic lesion, outside the uterus. Endometriotic lesion form from retrograde menstruation (menstrual fluid reflux through the fallopian tubes) but the precise pathogenesis remains unclear. There are no noninvasive biomarkers currently used in clinical care but they are essential to improve the diagnosis delay, currently estimated at 8 years. There is no specific treatment and pharmacological options are contraceptive. Within this project, we will use menstrual fluid as a relevant biological fluid for endometriosis. We will compare the gene expression profile of each of the cells contained in the menstrual fluid of women affected or not by endometriosis. We will look at the molecules that can be found outsides of these cells in the menstrual fluid. With thisinformation, we will used computational tools to identify candidate diagnostic biomarkers that differentiate endometriosis affected women from healthy controls. We will then validate the usefullness of these biomarkers in additional menstrual fluid samples from a total of 250 women. In parallel, we will generate 3D cellular models derived from the menstrual fluid cells of women with or without endometriosis. These 3D models will be cultivated in vitro with immune cells to better understand the interaction between the endometrial and immune cells. This will allow us to design and test new immunomodulatory treatments. Finally, we will also look for prognostic/predictive candidate biomarkers in two context : in response to surgery and in vitro fertilization (IVF). A prognostic biomarker could allow a better follow up of the disease after surgery (to monitor that it is not coming back for example). To identify such potential biomarkers, we will compare the gene expression profile in menstrual fluid cells obtained before and after the endometriosis surgery. A predictive biomarker for IVF may allow to predict the sucess of such procedure and potentially have some hypothesis for a lack of success. To identify such potential biomarkers, we will assess the gene expression profile in menstrual fluid cells obtained before an IVF procedure and compare the samples from women with a positive versus a negative pregnancy test following the IVF.
Diagnostic and prognostic/predictive biomarkers are essential to assess disease establishment, evolution and to choose the most appropriate treatment. This project will enhance our understanding of endometriosis pathophysiology as well as allow the study of menstrual blood, a relevant biological fluid for gynecology and reproductive disorders.
The ethical application to be allowed to collect menstrual blood from women with and without endometriosis has been submitted and approved. The enrolment of participants is ongoing (NCT06245512). The accurate processing of the menstrual blood samples has been defined and the first analyses are ongoing.