Evidence for Beneficial Effects of Voluntary Exercise in an Endometriosis‐Stress Animal Model

Abstract

Endometriosis is a chronic gynecological disorder characterized by peritoneal inflammation, infertility, chronic pelvic pain, fibrosis, and growth of endometrial tissue outside the endometrial cavity. In previous studies we found that exposure to stress exacerbates the development and severity of endometriosis. Exercise has been shown to confer beneficial effects in many chronic conditions. We previously demonstrated that exposure to voluntary exercise prior and after the induction of endometriosis in an animal model can improve the condition. However, it is unclear whether exercise can also alleviate the stress-induced exacerbation of endometriosis. Hypothesis Voluntary exercise interventions can promote and help to ‘realign/reset’ dysregulation of the brain-gut axis caused by psychological stress resulting in reduced symptoms in animals with endometriosis. Methods Endometriosis (Endo) was induced in female Sprague Dawley Rats by implanting four pieces of uterine tissue next to the intestinal mesentery on day 0, while Sham controls received sutures only. Abdominal circumference and BMI were measured and calculated respectively for all animals before surgery. All animals were exposed to water avoidance stress at day 14 after surgery for seven consecutive days (1hr/day). Endo (n=10) and Sham (n=10) controls received no exercise. Endometriosis-exercise (EEX; n=10) and sham-exercise (SHEX; n=10) had access to a running wheel after surgery until time of sacrifice (day 60). At sacrifice, the abdominal circumference and BMI was measured and calculated, and the developed vesicles and colon were collected and stored for future analysis. Results Exercised groups consumed more food when compared to their respective controls (Endo vs EEX p<0.001; Sham vs SHEX p<0.01) but tended to gain less weight overall. No difference was observed in the distance or speed travelled between EEX and SHEX. Endo had significantly higher percent of fat/body weight compared to sham groups (p<0.001), and this was reversed by exercise. Endo animals had significantly increased abdominal circumference (p<0.05) and BMI (p<0.05) at sacrifice compared to the day of surgery; these differences were not significant in the other groups. Endo animals developed vesicles in 75.0% of the implants with a total length of 11.08±1.74mm/animal and total vesicle weight of 0.12±0.02g/animal. No vesicles developed in Sham or SHEX. Exposure to exercise significantly decreased the number of vesicles that developed (42.5% p<0.05), as well as vesicle size (5.86±1.57mm, p<0.05), and weight (0.05±0.02g, p<0.05) per animal. Endo had increased colonic macroscopic damage compared to Sham (p<0.001), and exercise groups (p<0.001). Conclusions Our results suggest that voluntary physical activity might alleviate the aggravated endometriosis associated symptomatology which occurs during stress conditions. Overall, this study supports the potential for further investigation of voluntary exercise as a complementary therapy in patients with endometriosis.