Comparison the Effect of Metformin and Clomiphene Citrate on Sirtuin3 gene Expression in the Oocytes of Mice with Polycystic Ovary Syndrome

Oxidative stress (OS) is a common biological event in polycystic ovarian syndrome (PCOS), causing oocytes to undergo OS-induced changes. Sirtuin3 (Sirt3) has a critical role in oocyte maturation through the modulation of OS. In the current study, we compared the effects of metformin and clomiphene citrate on the expression of the Sirt3 gene in oocytes obtained from the mice, induced by PCOS. The induction of PCOS was performed by the single injection of estradiol valerate. The animals were divided into control, PCOS, metformin (500 mg/Kg), and clomiphene (18 mg/kg) groups. At the end of the experiment, the levels of LH and FSH were determined using the ELISA method. The ovarian tissues were evaluated histologically, and the expression of the Sirt3 gene was analyzed by the Real-time PCR. The induction of PCOS led to an increase in the ratio of LH/FSH elevation, the number of follicle atresia, as well as the presence of hydrated cysts. The results showed that both treatment regimens returned the altered parameters to the baseline values. The gene of Sirt3 was significantly (P < 0.001) reduced in the PCOS group compared to the control. Also, no significant difference was found in the expression of Sirt3 between clomiphene and PCOS group, whereas, in the metformin group, Sirt3 expression had the higher rate of expression in comparison with the PCOS group (P < 0.05). The administration of metformin and clomiphene showed that metformin is capable of preventing the downregulation of the Sirt3 gene in oocytes, collected from PCOS mice.