Role of microRNA-21 in the androgen-induced metabolic effects in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries. Epidemiological studies have shown that PCOS women present a significantly higher incidence of cardiovascular risk factors such as obesity, insulin resistance, dyslipidemia, and elevated blood pressure. In the US, up to 80% of PCOS women are obese and have insulin resistance. Effective therapeutic approaches to treat the metabolic dysfunction present in PCOS women are limited, and there is an urgent need for better therapeutic options. 

MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs that downregulate the expression of specific proteins. Several miRNAs are dysregulated in PCOS women, and a few have been implicated in PCOS metabolic manifestations. Although miRNAs are highly attractive therapeutic targets that are making their way into the clinic, the role of miRNAs as therapeutic agents to treat the metabolic dysfunction of PCOS remains unexplored. MicroRNA-21 (miR-21) is an attractive target because it is one of the most upregulated circulating miRNAs in PCOS subjects and experimental animal models of PCOS. miR-21 is highly expressed and dynamically regulated in multiple tissues, including adipose tissue, liver, and muscle. These tissues have been implicated in the metabolic dysfunction observed in PCOS.  

The main goal of this project is to study the role of miR-21 in hyperandrogenemia-induced obesity, insulin resistance, dyslipidemia, and increased blood pressure in a mouse model of PCOS. This highly significant and innovative project will establish the foundation for a novel therapeutic approach for the androgen-induced metabolic dysfunction observed in PCOS that, alone or in combination with other therapies, could reduce the cardiovascular risk factors in PCOS subjects leading to a reduction in cardiovascular events.