Regression of endometrial explants in a rat model of endometriosis treated with melatonin

Objective: To determine the antioxidant, antiinflammatory, and immunomodulatory effects of melatonin on endometrial explants, the distribution of cyclooxygenase-2 (COX-2), the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and levels of malondialdehyde (MDA) in the rat endometriosis model. Design: Prospective, placebo-controlled experimental study. Setting: Experimental surgery laboratory in a university department. Animal(s): Twenty-five rats with experimentally induced endometriosis. Intervention(s): Endometriosis was surgically induced in 25 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Four weeks later, three rats were killed and the remaining 22 rats given second-look laparotomies to identify and measure ectopic uterine tissue in three dimensions. After the second laparotomy, 4 weeks of vehicle and melatonin treatment were administered, then all of the rats were given a third laparotomy and killed. Main Outcome Measure(S): The volume and weight of the implants were measured. The remaining rats were randomly divided into two groups. In control group (group 1; n = 11:1 no medication was given. To the rats in melatonin-treated group (group 2; n = 11), 10 mg/kg a day of melatonin was administered intraperitoneally. Four weeks later, after the second laparotomy, the endometrial explants were reevaluated morphologically, and COX-2 expression was evaluated immunohistochemically and histologically. In addition, endometrial explants were analyzed for the antioxidant enzymes SOD, CAT, and MDA, a marker of lipid peroxidation. A scoring system was used to evaluate expression of COX-2 and preservation of epithelia. Result(s): The pretreatment and posttreatment volumes within the control group were 135.9 +/- 31.5 and 1.29.4 +/- 28.7, respectively. The mean explant volume was 141.4 +/- 34.4 within the melatonin group before the treatment and 42.9 +/- 14.0 after 4 weeks of treatment. There was a statistically significant difference in spherical volumes (129.4 +/- 28.7 versus 42.9 +/- 14.0 mm) of explant weights (155.8 +/- 27.1 versus 49.6 +/- 19.5 mg) and COX-2 positivity (91% versus 18.1%) between groups after the third laparotomy. In the melatonin-treated group, the endometrial explant levels of MDA statistically significantly decreased and activities of SOD and CAT significantly increased when compared with the control group. The epithelia showed statistically significantly better preservation in the control group when compared with the melatonin-treated group (2.54 +/- 0.52 versus 0.63 +/- 0.50). Conclusion(s): Melatonin causes regression and atrophy of the endometriotic lesions in rats.