Molecular mechanisms of Polyendocrine Metabolic Ovarian Syndrome and identification of novel druggable targets for...

Polyendocrine Metabolic Ovarian Syndrome (PMOS) is a heterogeneous disorder that mainly affects women of reproductive age. Genetic predisposition, insulin resistance, androgen excess, inflammation, mitochondrial dysfunction, and changes in gut microbial composition were notable contributors to the prognosis of PMOS. Several genetic variations, including mutations, polymorphisms, and variations in gene regulation, have been identified that predispose individuals to PMOS. A complex network involving metabolic, hormonal, and inflammatory pathways plays a major role in disease progression. To identify the key genetic domains, we employed a network-based cluster analysis, which revealed that insulin signalling, mitochondrial function, and steroidogenesis could be critical in disease progression. Many signalling pathways and targets have been overlooked in developing novel therapeutics for PMOS, including potential opportunities for drug repositioning. In this review, to the best of our knowledge, we highlight molecular pathways, targets, and molecules that could be utilised to develop novel therapeutics for PMOS. This review also provides new insights into the pathogenesis of PMOS, potentially leading to more effective management of the condition.