Endometriosis Transcriptomic Cell Atlas

Establishing an Endometriosis Transcriptomic Cell Atlas to Decipher the Pathophysiological Role of Stem Cells and Estrogens in the Disease

Endometriosis is an estrogen-dependent, chronic inflammatory gynecologic disease affecting women of reproductive age, with a therapeutic wandering of 6 to 10 years. A better understanding of the initiation phase is a major challenge to improve diagnosis and treatment. The most widely accepted hypothesis to explain the formation of endometriotic lesions is the tubal retrograde reflux during menstruation. However, only 10% of the reproductive age women will develop endometriosis while 90% of women experience retrograde menstruation. This raises the question of the stem cells present in the endometrium and menstrual reflux of these patients, but also of both the peritoneal microenvironment and the estrogenic local signaling which allow the implantation of these lesions.

Using tissues collected at different phases of menstrual cycle in healthy women and patients operated for endometriotic lesions, 3 main objectives :

1. To characterize cellular heterogeneity between eutopic endometrium and ectopic lesions in parallel with peritoneal fluid to identify potential stem cells and the immune microenvironment in order to find new biomarkers (using a combination of unbiased transcriptomic, spectral flow cytometry and multiplex imaging analysis)
2. To develop organoid models that integrate peritoneal fluid elements (supernatant and/or cells) to clarify stem cell properties/characteristics and their supportive environment
3. To leverage the use of these endometrial derived-organoids to functionally study the differential influence of estrogen signaling in women with or without endometriosis

Inclusion Criteria:

• Patients over 18 and under 45 years of age
• Patients with multiple endometriosis sites (superficial, deep and endometriomas) with an indication for surgery to treat disabling painful symptoms and stage III or IV endometriosis in the context of infertility.
• Healthy patients including those operated on between the ages of 18 and 45 for tubal ligation
• Healthy patients operated on between the ages of 18 and 45 for hysterectomies for benign causes other than endometriosis or adenomyosis
• Patients operated on strictly at the time of menstruation
• Participants who have not been on hormonal treatment for 2 months
• Participant having signed the free and informed consent form
• Membership of a Social Security scheme or equivalent

Exclusion Criteria:

• Patients with endometriosis non-surgically treated
• Patients with endometriosis receiving hormonal treatment at the time of surgery or having received hormonal treatment in the 2 months prior to surgery
• Patients with adenomyosis only
• Healthy non-endometriotic patients undergoing hysterectomy for infectious or malignant causes
• Patients benefiting from a legal protection measure (guardianship, curatorship, safeguard of justice)
• Patients with positive serology for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B (HBV) and hepatitis C (HCV)