Current Issue

Volume 20, Number 2, Summer 2018, Serial Number: 78 Pages: 231-243

Effect of (R)-(+) Pulegone on Ovarian Tissue; Correlation with Expression of Aromatase Cyp19 and Ovarian Selected Genes in Mice


Rohiyeh Souldouzi, D.V.M, 1, Mazdak Razi, D.V.M., Ph.D, 1, Ali Shalizar Jalali, D.V.M., Ph.D, 1, *, Ghader Jalilzadeh-Amin, D.V.M., D.V.Sc., 2, Saeedeh Amani, D.V.M., 1,
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
*Corresponding Address: P.O. Box: 5756151818 Department of Basic Sciences Faculty of Veterinary Medicine Urmia University Urmia Iran Email:a.shalizar@urmia.ac.ir

Abstract

Objective

Pulegone (PGN) is a monoterpene ketone, whose metabolites exert several cytotoxic effects in various tissues. The present study was conducted in order to evaluate the (R)-(+) PGN-induced alterations in ovarian aromatization, proto-oncogenes and estrogen receptorα (ERα) and ERβ receptors expressions.

Materials and Methods

In this experimental study, mature albino mice were divided into experimental (received 25 mg/kg, 50 mg/kg and 100 mg/kg PGN, orally for 35 days) and control (received 2% solution of Tween 80 as a PGN solvent, orally) groups. The mRNA levels of Erα, Erβ, p53, Bcl-2, and cytochrome p450 (Cyp19) as well as ovarian angiogenesis were analyzed through reverse transcription polymerase chain reaction and immunohistochemical techniques, respectively. Moreover, apoptosis of follicular cells, serum estrogen and progesterone levels and mRNA damage were investigated via using terminal transferase and biotin-16-dUTP staining, electrochemilunescence and fluorescent microscopy methods, respectively.

Results

The PGN reduced Erα, Erβ and Cyp19 expression at 50 mg/kg and 100 mg/kg doses, while significantly elevating p53 and reducing Bcl-2 expression. Finally, PGN impaired ovarian angiogenesis, increased apoptosis, elevated follicular atresia and reduced serum levels of estrogen and progesterone.

Conclusion

Chronic exposure to PGN (50 mg/kg and 100 mg/kg), severely affects ovarian aromatization, proto- oncogenes mRNA levels and expression of ERs.