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 receptoralpha [ER alpha] and ER beta 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 Er alpha, Er beta, 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 Er alpha, Er beta 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