The investigation of the effect of metformin and pioglitazon on the ovum quality in polycystic ovary syndrome rat model

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among women of reproductive age. Particularly obesity is a serious problem in a large proportion of PCOS patients and the effects of weight gain on ovum quality are not fully determined. In our study, we aimed to investigate the effects of monotherapy and combination therapy of metformin and pioglitazone on hormonal parameters and gene expressions in ovum development in rat which PCOS model was produced with testosterone propionate and high fat diet. In this study, 50 female Wistar Albino rats aged 21 days were used. These fifty female rats were divided into five experimental groups with ten rats in each group including control group, PCOS group (i.m injection of 10 mg/kg/day testosterone propionat and % 60 fat diet for 90 days), PCOS + metformin treated (300 mg/kg/day for 30 days), PCOS + pioglitazone treated (30 mg/kg/day, for 30 days), PCOS + metformin + pioglitazone treated. After decapitation at the end of 90 days, the ovarian tissues of the rats were removed and it is retained for histological and molecular genetic analysis. Routine hormone profile, glucose, cholesterol, HDL, VLDL and triglyceride levels were measured in serum samples. SYCP2, CYBB, GADD45A, BAX, FAS, FASL, BCL2L1, CASP2, BIRC2 BECN1, VEGFA, GAP43, MAPK1 genes were analyzed by qRT-PCR. Plasma progesterone level significantly decreased and testosterone significantly increased in the PCOS induced rats when compared with control group. Glucose levels in the PCOS group were also significantly increased. When the treatment groups were compared with the PCOS group, testosterone were significantly decreased only in the pioglitazone group. Histologically, it was observed that cystic follicular structures were increased in PCOS group. Treatment of PCOS rats with metformin and pioglitazone resulted in reduction of the number of cystic follicles when compared to untreated PCOS rats but drug treatments showed no superiority to each other in this respect. OLR1583 and Bcl2L1 genes were significantly increased and SYCP2, CYBB, GADD45A, BAX and FasL genes were significantly decreased in all PCOS groups when compared to the control group. Our study is the first study to investigating the effects of metformin and pioglitazone treatment in the obese PCOS model. Drugs have been identified as having considerable therapeutic effects, particularly on ovarian morphology and hormone profiles. Molecular genetic analysis did not support these findings, although histological findings indicate that drug treatment has positive effects on ovarian morphology. SYCP2 gene is responsible for meiosis, CYBB gene is responsible for respiratory reaction in mitochondria, GADD45A gen is responsible for repair on genom and decrease in these gene expressions continued in the treatment group. BAX and FASL gene expressions from the proapoptotic genes were significantly decreased in the PCOS group compared to the control group. However, the expression of the BCL2L1 gene from the antiapoptotic genes which were significantly higher than the control does not support an increased apoptosis. On the contrary, apoptosis is decreased in the group of PCOS but this decline is normalized in the treatment groups.In particular, there is a need for more detailed molecular genetic analyzes to reveal the function of these genes on ovary. Key Words: Polycystic ovary syndrome, metformine, pioglitazone, oocyte quality