Microsatellite DNA assays reveal an allelic imbalance (loss of heterozygosity) in p16 (Ink4), GALT, p53, and APOA2 loci in patients with endometriosis and in stage II of endometriosis (79). Another report found a loss of heterozygosity in 28% of endometriotic lesions at one or more sites: chromosomes 9p (18%), 11q (18%), and 22q (15%) (73).
Although retrograde menstruation appears to be a common event in women, not all women who have retrograde menstruation develop endometriosis. The immune system may be altered in women with endometriosis, and it is hypothesized that the disease may develop as a result of reduced immunologic clearance of viable endometrial cells from the pelvic cavity (80,81). Endometriosis can be caused by decreased clearance of peritoneal ﬂuid endometrial cells resulting from reduced natural killer (NK) cell activity or decreased macrophage activity (82). Decreased cell-mediated cytotoxicity toward autologous endometrial cells is associated with endometriosis (82–86). These studies used techniques that have considerable variability in target cells and methods (87,88). Whether NK cell activity is lower in patients with endometriosis than in those without endometriosis is controversial. Some reports demonstrate reduced NK activity and others found no increase in NK activity in women with moderate to severe disease (84– 86,89–94). There is great variability in NK cell activity among normal individuals that may be related to variables such as smoking, drug use, and exercise (87).
In contrast, endometriosis can be considered a condition of immunologic tolerance, as opposed to ectopic endometrium, which essentially is self-tissue (80). It can be questioned why viable endometrial cells in the peritoneal ﬂuid would be a target for NK cells or macrophages. Auto-transplantation of blood vessels, muscles, skin grafts, and other tissues is extremely successful (83–85). There is no in vitro evidence that peritoneal ﬂuid macrophages actually attack and perform phagocytosis of viable peritoneal ﬂuid endometrial cells. High-dose immunosuppression can increase slightly the progression of spontaneous endometriosis in baboons (95). There is no clinical evidence that the prevalence of endometriosis is increased in immunosuppressed patients. The fact that women with kidney transplants, who undergo chronic immunosuppression, are not known to have increased infertility problems can be considered indirect evidence that these patients do not develop extensive endometriosis.