This family consists of 5 ligands, PDGFA, PDGFB, PDGFAB, PDGFC, and PDGFD, and 2 receptors, PDGFRα and PDGFRB ( 6). The platelet-derived growth factor (PDGF) family plays a critical role in the recruitment of pericytes to new vessels ( 4, 5). This family comprises the agonist ANGPT1, the antagonist ANGPT2, and the receptor tunica interna endothelial cell kinase (TEK) ( 3). Another family of angiogenic factors is the angiopoietin (ANGPT) family, which is mainly involved in the regulation of vessel stability and permeability. The main angiogenic factor is the vascular endothelial growth factor (VEGF), which mediates endothelial cell migration and proliferation ( 3). Several angiogenic factors, acting in a coordinated manner, are responsible for the correct formation of new blood vessels ( 3). The angiogenic process needs to be tightly regulated to accomplish the formation of competent vasculature. In addition, PCOS is characterized by abnormalities in angiogenesis. Its symptoms are heterogeneous and range from chronic anovulation, oligo- or amenorrhea, and hyperandrogenism to obesity and insulin resistance ( 1, 2). Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than 5% of women of reproductive age. These results open new insights into the study of metformin action not only in glucose metabolism but also in ovarian dysfunction in PCOS women.

The improvement in ovarian angiogenesis is likely to restore the accumulation of small follicles observed in PCOS rats and to reduce cyst formation, thus improving follicular development and the percentage of corpora lutea. We also found an improvement in follicular development, with a lower percentage of small follicles and cysts and a higher percentage of antral follicles and corpora lutea after metformin administration. These effects could take place, at least in part, through a decrease in the levels of serum insulin. We found that metformin was able to restore the increased levels of vascular endothelial growth factor, angiopoietin (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived growth factor B and platelet-derived growth factor D observed in the dehydroepiandrosterone-treated rats. In the present study, we used a dehydroepiandrosterone-induced PCOS rat model to analyze the effect of metformin administration on ovarian angiogenesis. Besides its metabolic effects, metformin has been shown to improve ovulation, pregnancy and live birth rates in PCOS patients.

Metformin has been introduced in the treatment of PCOS to manage insulin resistance and hyperglycemia. Among other heterogeneous symptoms, PCOS is characterized by abnormalities in angiogenesis.

10mm female slideas