Dissertation committee:
Κόντζογλου Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργόπουλος Σωτήριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αντωνίου Ευστάθιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δημητρούλης Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μπακογιάννης Χρήστος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βερύκοκος Χρήστος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καλαμπόκας Θεόδωρος, Επίκουρος Καθηγητής, Ιατρικής Σχολής, ΕΚΠΑ
Summary:
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.
Keywords:
Angiogenesis, Mice, Peroxisome proliferator, Ppar-alpha, Endometriosis