Angiogenic and Inflammatory Alterations of Endometriotic Lesions in a Transgenic Animal Experimental Model With Loss of Expression of PPAR-Alpha Receptors

Vasilios Pergialiotis, Nikolaos Zarkadoulas, Kallirroi Goula, Maximos Frountzas, Fotino Antoniadou, Dimitrios Dimitroulis, Dimitrios Vlachos, Aggeliki Papapanagiotou, Angeliki Papapanagiotou, Christos Verikokos, Despoina N Perrea, Δέσποινα Περρέα, Konstantinos Kontzoglou
Cureus · 2022 · vol. 14(10) , pp. e30290 · doi:10.7759/cureus.30290 · PMID:36381820 · PMC9650956 · W4306174440
article OA: gold CC0 ⤵ 2 in-corpus citations
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Abstract

INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) have been proposed as a medical treatment against endometriosis in preclinical and clinical studies. Their effect seems to be triggered through the suppression of angiogenesis. In the present study, we used a transgenic animal model with a loss of expression of PPAR-alpha receptors to examine their effect on the course of surgically induced endometriotic lesions. METHODS: Ten C57BL/6 mice that served as controls and 10 B6;129S4-PPARatm1Gonz/J t transgenic mice characterized by absolute loss of expression of PPAR-alpha receptors were used for induction of endometriosis with a previously described surgical technique. RESULTS: Five animals (50%) exhibited abundant endometriotic crypts in the control group whereas only one (10%) animal in the transgenic experimental group had a similar pathological image. Neo-vascularization significantly differed among the two groups (p=0.034) favoring the control group as it was extremely limited in half of the PPAR-alpha null animals. The median inflammation score was 2.5 (1-4) in the P B6;129S4-PPARatm1Gonz/J group, whereas it was minimal, 1 (0-2), in the C57BL/6 group. However, these differences were not statistically significant (p=0.101). The fibroblastic activity was also very limited in the PPAR-alpha-deficient model, whereas animals belonging to the control group exhibited an intermediate increase of this index (p=0.022). CONCLUSION: Surgically induced endometriotic implants in animals with loss of expression of PPAR-alpha receptors exhibit significant differences in their pathology compared to lesions induced in control animals. This information suggests that PPAR-alpha receptors have a significant impact on the course of the disease, indicating that they may serve as potential targets for future medical therapies.

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