Differential Regulation of Vitamin D Receptor Expression and Macrophage Infiltration by Stress in an Animal Model of Endometriosis

Prior studies from our laboratory have shown that stress can exacerbate the severity of endometriosis, a chronic gynecological disorder. The vitamin D receptor (VDR), expressed in cycling endometrium, is associated with anti-proliferative and anti-inflammatory effects; however its role in endometriosis is unclear. Stress might affect VDR via immune disruption, thus influencing macrophage infiltration. Aim Investigate the impact of stress on VDR expression and macrophage infiltration in an animal model of endometriosis. METHODS: Endometriosis was surgically induced in female Sprague-Dawley rats. Rats were exposed to either uncontrollable, controllable or no stress for 10 days. At sacrifice (day 60) all rats were examined for cysts. Cellular infiltration and VDR expression was assessed by immunofluorescence and immunohistochemistry. RESULTS: Uncontrollable stress increased uterine neutrophil infiltration and the size and number of cysts compared to no stress, while controllable stress showed no difference. Uncontrollable stress also increased macrophage infiltration (p<0.01) and VDR expression in both the glands and stroma of cysts. This was abrogated in the controllable stress group. VDR expression on macrophages did not differ between groups. In contrast VDR expression in the uterine glands and stroma was down regulated by stress. CONCLUSION Stress exacerbates development of cysts in an animal model of endometriosis through mechanisms that include macrophage recruitment and VDR regulation. R15AT006373 & R25GM082406