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; Christos Verikokos; Despoina N Perrea; Konstantinos Kontzoglou

doi:10.7759/cureus.30290

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

Cureus. 2022 Oct 14;14(10):e30290. doi: 10.7759/cureus.30290. eCollection 2022 Oct.

Affiliations

¹ First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, GRC.
² Laboratory of Experimental Surgery and Surgical Research N.S. Christeas, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.
³ Department of Pathology, Alexandra Hospital, Athens, GRC.
⁴ First Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.
⁵ Second Department of Surgery, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.
⁶ First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.
⁷ Department of Biological Chemistry, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.
⁸ Second Department of Surgery, Laikon Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.
⁹ Laboratory of Experimental Surgery and Surgical Research, National and Kapodistrian University of Athens School of Medicine, Athens, GRC.

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-PPARa^{tm1Gonz/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-PPARa^tm1Gonz/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.

Keywords: 129s4-pparatm1gonz/j; angiogenesis; endometriosis; mice; peroxisome proliferator; ppar-alpha.

Grants and funding

This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project “Reinforcement of Postdoctoral Researchers – 2nd Cycle (MIS 5033021)", implemented by the State Scholarships Foundation (IKY)