Metformin Decreases the Expression of VEGF-A and CTGF-1 and Improves Histological, Ultrastructural and Hormonal Changes in Adult Rat Polycystic Ovary

In this study we explored the possible beneficial role of metformin (MT) treatment on the hormonal, histological and ultrastructural changes in testosterone propionate induced polycystic ovary (PCO) in rats. A total of 45 female adult rats were divided into control, PCO and MT-PCO groups. After 28 days of treatment, blood samples were taken for estimation of glucose, insulin, sex hormones as well as insulin resistance (IR) and insulin sensitivity (IS) indices (HOMA-IR & QUICKI-IS). Ovarian tissues were processed for light and electron microscopic studies. Also, immunohistochemical stains were done for detection of vascular endothelial growth factor-A (VEGF-A) and connective tissue growth factor-1 (CTGF-1). The PCO group showed a decrease in follicle number with a predominance of cystic follicles, absence of corpora lutea, decrease in the thickness of granulosa cells and increased thickness of theca interna cells layers, hypercellularity of interstitial stroma, as well as increased expression of VEGF-A and CTGF-1. Ultrastructurally, signs of granulosa cell degeneration and luteinization of theca interna cells were noted. Additionally, an increase in the serum concentration of estrogen, testosterone, insulin, IR and a decrease in progesterone and IS were also observed. MT treated PCO group showed improvement of the above-mentioned changes. These data provide new insight about the promising effect of MT in treatment for PCOS associated infertility.