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

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.

Grant Number: 5R16GM149365-03
NIH Institute/Center: NIH
Principal Investigator: Caroline Appleyard