The Enteric Glia as a Possible Target for Symptom Relief in Endometriosis

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Endometriosis, a chronic painful gynecological disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity, is characterized by peritoneal inflammation, fibrosis, adhesions, and ovarian cysts. Women with endometriosis often present gastrointestinal symptoms independent of lesion localization. Enteric glial cells (EGCs) are astrocyte-like cells that are vital to the enteric nervous system and play a role in gut diseases. The role of intestinal glia in endometriosis is unknown; however, a bidirectional relationship between the EGC and immune cells in the modulation of the inflammatory response and pain sensitization is postulated. Enteric glia can produce an endogenous ligand for peroxisome proliferator activated receptor gamma (PPAR) with anti-inflammatory activity. PPAR agonists in endometriosis animal models reduce vesicle size. The study team’s previous work has demonstrated that exercise can increase expression and activity of PPAR, while reducing vesicle size and development. The main objective is to examine the role of EGC in the pathophysiology of endometriosis with the long-term goal of finding new therapeutic targets. The study team hypothesizes that endometriosis-induced immune activation is regulated by ECG which promotes and maintains chronic inflammation, and that this can be reversed by non-pharmacological complementary interventions. Aim 1 will determine how endometriosis impacts the enteric glia and how this correlates with pain. Aim 2 will elucidate whether the beneficial effects of interventions, such as exercise and environmental enrichment, are mediated by PPAR. Rationale: complementary interventions will impact the enteric glia via parasympathetic activation, shifting it from the endometriosis-induced, pro-inflammatory phenotype to an anti-inflammatory one, decreasing proinflammatory cytokine release and oxidative stress. Successful outcomes could explain chronic pelvic inflammation and gastrointestinal symptoms and provide a novel target. This study will contribute to the goals of the SuRE program by sustaining the research excellence of the PI and strengthening the institutional research environment. This study will provide graduate and undergraduate students at various levels with opportunities in multidisciplinary research areas to encourage their continued involvement in biomedical sciences research and stimulate their interest in novel integrative interventions.