Updates on Molecular Targets and Epigenetic-Based Therapies for PCOS

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2023-03, Vol.30 (3), p.772-786
• Main Authors: Smirnov, Viktor V., Beeraka, Narasimha M., Butko, Dmitry Yu, Nikolenko, Vladimir N., Bondarev, Sergey A., Achkasov, Evgeniy E., Sinelnikov, Mikhail Y., Vikram, P. R. Hemanth
• Format: Article
• Language: English
• Subjects: Embryology; Female; Humans; Hyperandrogenism - drug therapy; Infertility - drug therapy; Insulin Resistance; Medicine; Medicine & Public Health; Metformin - therapeutic use; Obstetrics/Perinatology/Midwifery; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Reproductive Medicine; Review
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1007/s43032-022-01013-x

Polycystic ovarian syndrome (PCOS) can cause infertility in females due to hyperandrogenism and neuroendocrine abnormalities. The aim of this study is to decipher the impact of endocrine variables, hyperandogenism, insulin resistance, oxidative stress, and dietary conditions in PCOS conditions, subsequently to depict the role of epigenetic factors relative to phenotypic manifestations in PCOS conditions. We have reviewed several metabolic milieus pertinent to PCOS conditions. Comparative efficacies of various PCOS therapies, and recent clinical recommendations for the effective management of PCOS and role of metabolic/endocrine variables in PCOS conditions were described. Comparative therapeutic effects were vividly delineated according to the variable pathophysiology and internal variables during PCOS syndrome on the female body through the formation of cascade of endocrine pathology, which affects working capacity and fosters redox stress-induced cardiovascular, neural, and liver abnormalities. GLP-1 agonists, insulin sensitizers (metformin), and diet and exercise regimens efficacy were explained in enhancing the fertility outcomes among the overweight or obese females with PCOS. Comprehensive appraisal of DNA methylation as epigenetic changes and the manifestations of methylated genes in PCOS conditions were discussed particularly to screen novel molecular targets for developing efficient diagnostic indicators for predicting PCOS risk or its progression. Due to the reversible nature of epigenetic modifications, it is possible to screen the “druggable” regions to target or to correct abnormalities in the gene expression subsequently to develop chromatin-modifying therapies against PCOS.