Uncontrollable stress causes downregulation of CCL2 in colon of the endometriosis rat model (898.4)

Background: Endometriosis is characterized by the growth of endometrial tissue in areas such as the peritoneal cavity and colon causing pain and discomfort. We have previously demonstrated that rats with explants of endometrial tissue in the peritoneal cavity subjected to stress showed a significant increase in the size of endometrial lesions. Chemokine ligand 2 (CCL2) has been found to be increased in plasma in women with endometriosis perhaps contributing to the inflammatory process but the effects of stress on this cytokine are still unclear. Aim: Examine the relationship between CCL2 expression and stress in a rat model of endometriosis. Methods: Endometriosis was surgically induced in female Sprague‐Dawley rats by transplanting uterine tissue onto the intestinal mesentery. Sham rats had sutures only. Animals were exposed to either an uncontrollable (ENDO‐UN) or controllable (ENDO‐C) stress protocol for 10 days, or no stress (ENDO‐NS). At sacrifice (day 60), all rats were examined for presence of endometrial cysts, and colons were collected for mRNA extraction and histology analysis. The relative expression of CCL2 was measured by PCR, and macrophage numbers were determined by immunofluorescence for CD68. Results: As might be expected CCL2 transcript levels were higher in colonic tissue from animals with ENDO‐NS compared to sham however they were significantly decreased in ENDO‐UN (p<0.05). mRNA expression of CCL2 positively correlated with CD68 positive cells (p<0.05). Surprisingly, higher levels of corticosterone and microscopic damage accompanied the lower levels of CCL2 in stressed animals. Conclusion: In this model uncontrollable stress decreases colonic CCL2 expression, possibly via corticosterone‐induced immunosuppression. It is unclear whether decreased CCL2 and/or increased corticosterone levels induced by stress contribute to an increased severity of colonic damage. Grant Funding Source : R15A006373, RR003050/MD007579