Souldouzi Rohiyeh, Razi Mazdak, Shalizar Jalali Ali, Jalilzadeh-Amin Ghader, Amani Saeedeh
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Cell J. 2018 Jul;20(2):231-243. doi: 10.22074/cellj.2018.4798. Epub 2018 Mar 18.
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.
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.
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.
Chronic exposure to PGN (50 mg/kg and 100 mg/kg), severely affects ovarian aromatization, protooncogenes mRNA levels and expression of ERs.
长叶薄荷酮（PGN）是一种单萜酮，其代谢产物在多种组织中发挥多种细胞毒性作用。进行本研究以评估（R）-（+）PGN诱导的卵巢芳香化、原癌基因以及雌激素受体α（ERα）和ERβ受体表达的变化。
在本实验研究中，将成熟的白化小鼠分为实验组（分别口服25mg/kg、50mg/kg和100mg/kg的PGN，持续35天）和对照组（口服2%吐温80溶液作为PGN溶剂）。分别通过逆转录聚合酶链反应和免疫组织化学技术分析Erα、Erβ、p53、Bcl-2和细胞色素p450（Cyp19）的mRNA水平以及卵巢血管生成情况。此外，分别使用末端转移酶和生物素-16-dUTP染色、电化学发光和荧光显微镜方法研究卵泡细胞凋亡、血清雌激素和孕酮水平以及mRNA损伤情况。
PGN在50mg/kg和100mg/kg剂量时降低了Erα、Erβ和Cyp19的表达，同时显著提高了p53的表达并降低了Bcl-2的表达。最后，PGN损害了卵巢血管生成，增加了细胞凋亡，提高了卵泡闭锁率，并降低了血清雌激素和孕酮水平。
长期暴露于PGN（50mg/kg和100mg/kg）会严重影响卵巢芳香化、原癌基因mRNA水平和雌激素受体的表达。
