Effect of a statin on an in vitro model of endometriosis

Objective: To determine the inhibitory effect of a statin on angiogenesis in a three-dimensional (3-D) culture of human endometrial fragments in vitro. Angiogenesis has been proposed as an important mechanism in the pathogenesis of endometriosis, and statins (3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitors) have been shown to have anti-inflammatory and anti-angiogenic activity. Design: Experimental in vitro study of human endometrial biopsies and 3-D culture in fibrin matrix. Setting: Research laboratory at a university-affiliated infertility center. Patient(S): Forty-six normal ovulating women undergoing infertility treatment. Intervention(S): Endometrial samples obtained from the fundus of the uterine cavity were minced, and the fragments were placed in a three-dimensional fibrin matrix culture system. Main Outcome Measure(s): Presence or absence of proliferation of stromal cells and invasion of the fibrin matrix, presence or absence of vessel sprouting, and immunohistochemical characterization of cellular components. Result(s): During the 1st week of culture, invasion of stromal cells into the fibrin matrix occurred in the control group and in some wells outgrowths were observed. After 2 weeks, endometrial glands were observed in the outgrowths at a distance from the main tissue and were growing in conjunction with new vessel formation until the end of culture period. A concentration-dependent effect of lovostatin was seen on cell growth and angiogenesis in the experimental groups. In the presence of 5 and 10 mu M of statin, angiogenesis was abolished, and cell proliferation was inhibited. In the presence of 1 mu M of lovastatin, angiogenesis was reduced, but cell proliferation was not affected. Conclusion(s): The statins were shown to be effective in inhibiting the mechanisms of cell proliferation and angiogenesis in an experimental model for the development of endometriosis-like tissue.