Peroxisome proliferator-activated receptor γ partially regulates the beneficial effects of voluntary wheel exercise in a rat animal model of endometriosis

Myrella L. Cruz, Luis A. Rivera, Ricardo E. Nunez-Reyes, Alanis P. Mercado-Hernandez, Derick B. Rivera-Rodriguez, James P. Torres-Pirela, Juliette M. Wolpert-Gaztambide, Vivianka Y. Ramos-Plaza, Annelyn Torres-Reverón, Caroline B. Appleyard
In: Journal of Endometriosis and Pelvic Pain Disorders · 2026 · doi:10.1177/22840265261497323 · W7223455459
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Blocking PPAR-γ signaling in rats with endometriosis abolished the exercise-induced reduction of vesicle development and colonic damage, indicating that PPAR-γ mediates these beneficial effects of voluntary wheel running.

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Abstract

Introduction: Voluntary physical activity reduces lesion development and inflammatory parameters in experimental endometriosis, though the mechanisms remain unclear. Peroxisome proliferator-activated receptor γ (PPAR-γ), a regulator of inflammation and nociception, may mediate these effects. We previously observed PPAR-γ overexpression in lesions of endometriosis animals and hypothesized that it underlies exercise-induced benefits. Methods: Adult female Sprague-Dawley rats were randomized to three groups ( n = 12/group): endometriosis-vehicle, endometriosis-vehicle + exercise, or endometriosis + PPAR-γ antagonist + exercise. Endometriosis was induced by suturing four uterine horn fragments on the intestinal mesentery (day 0). Exercised animals had continuous access to a running wheel. Pain behaviors (Von Frey, hot plate) were assessed, and vesicles, blood, peritoneal fluid, and tissues were collected on day 61. Results: Exercised rats had higher food consumption ( p < 0.001) without differences in body weight at sacrifice, and a reduced fat-to-body weight ratio ( p < 0.0001). All groups showed higher pain sensitivity after surgery, unaffected by PPAR-γ antagonism. Exercise significantly reduced vesicle development and colonic damage compared to the non-exercised group, while these effects were abrogated by the PPAR-γ antagonist. Serum MIP3 alpha levels increased in exercised rats (p<0.05), with no significant differences in other cytokines. Conclusion: Our results indicate that PPAR-γ signaling contributes to the beneficial effects of exercise on endometriotic lesion growth.

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