Mitochondrial dysfunction: An emerging link in the pathophysiology of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by irregular menstrual cycles, hyperandrogenism and subfertility. Due to its complex manifestation, the pathogenic mechanism of PCOS is not well defined. Cumulative effect of altered genetic and epigenetic factors along with environmental factors may play a role in the manifestation of PCOS leading to systemic malfunction. With failure of genome-wide association study (GWAS) and other studies performed on nuclear genome to provide any clue for precise mechanism of PCOS pathogenesis, attention has been diverted to mitochondria. Mitochondrion plays an important role in cellular metabolic functions and is linked to Insulin Resistance (IR). Recently, increasing reports suggest that mitochondrial dysfunction may be a contributing factor in the pathogenesis of PCOS. Hence, in this review, we have discussed mitochondrial biology in brief and emphasizes on genetic and epigenetic aspects of mitochondrial dysfunction studied in PCOS women and PCOS-like animal models. We also highlight underlying mechanism behind mitochondrial dysfunction contributing to PCOS and its related complications such as obesity, diabetes, cardiovascular diseases, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and cancer. Furthermore, contrasting remarks against involvement of mitochondrial dysfunction in PCOS pathophysiology have also been presented. This review enhances our understanding in relation to mitochondrial dysfunction in the etiology of PCOS and stimulates further research to explore a clear link between mitochondrial dysfunction and PCOS pathogenesis and progression. Understanding pathogenic mechanisms underlying PCOS will open new windows to develop promising therapeutic strategies against PCOS.