Endometriosis results from the mislocalization of cells that usually form the uterine lining, to ectopic locations. The condition can be asymptomatic, but for 10% of women in their reproductive years, it is associated with pelvic pain, fatigue, and irregular or heavy periods. Whether or not it produces symptoms, endometriosis can impair fertility and increase the likelihood of miscarriage and stillbirth in women who become pregnant. Mislocalized cells often form ectopic lesions, also called implants or nodules, on organs within the pelvic cavity, including the ovaries, intestines and bladder. Surgery and drugs are used to reduce the extent of lesions, to promote fertility and to relieve pain, but endometriosis is often recurring and can precipitate ovarian epithelial tumors.
Endometriosis is mediated partly by the immune system but very few endometriosis antigens have been identified. The cell surface glycoprotein, mucin 1 or MUC1, is a known ovarian tumor-associated antigen that is present in ectopic lesions of ovarian endometriosis. However, the role of MUC1 expression in endometriosis and its potential as a biomarker for ovarian cancer are unknown.
Here, the authors use double transgenic MUC1Kras mice, with inducible ovarian endometriosis, to study changes in MUC1 expression during progression to endometriosis. The mice develop benign, MUC1-positive ovarian lesions that closely resemble human endometriosis. MUC1 expression in the affected ovaries increases significantly as lesions develop, stimulating the production of MUC1-specific antibodies. High IgM and IgG antibody titers appear early in the disease process and are maintained. During the later stages of disease, MUC1Kras mice, like women with the disease, show an expansion of immunosuppressive Foxp3+ CD4 regulatory T cells in the draining lymph nodes. The authors suggest that developing tolerance to MUC1 during endometriosis may inhibit immune competence and enable cancer progression.
Implications and future directions
The authors describe and characterize an animal model of human endometriosis. The pattern of MUC1 expression and its impact on the immune system of the host should facilitate the development of novel immune-based approaches. MUC1Kras mice could also further clarify the role of MUC1 in endometriosis and provide an in vivo platform for testing MUC1 vaccines to treat endometriosis and prevent ovarian cancer.