PCOS and genetics: Exploring the heterogeneous role of potential genes in ovarian dysfunction, a hallmark of PCOS – A review

Abstract

PCOS is an endocrine disorder that affects women of reproductive age. The root of PCOS is ovarian dysfunction, which presents as hormonal disturbances affecting normal ovarian function to cause the symptoms and complications of the disease. This dysfunction causes symptoms like impaired maturation of follicles and disorders of various origins with multiple treatment regimens that are not always clear. Therefore, the present review mainly concentrates on the genetic level of ovarian dysfunction of PCOS. The articles were identified through a vigorous literature search where search engines such as PubMed, Google Scholar, databases, and Science Direct were used, and the articles published from 2015 to 2025 were referred. We identified that the key genes involved in the ovarian dysfunctions in PCOS include CYP11A1, CYP17A1, CYP19A1, AR, FSHR, LHCGR, AMH, INSR, SHBG, IRS1, GATA4, ADIPOQ, YAP1, TCF7L2, and DENND1A, which play a role in gonadotropin action, steroidogenesis, and folliculogenesis. Furthermore, epigenetic factors and miRNAs miR-93, 222, 155, 146a, 132, 320, 27a, 483, 21, 378, 17–92 Cluster, and 375, 221 are also involved in it. Abnormal expression of these genes is known to play a critical role in the etiology and pathogenesis of PCOS. Present treatment includes the use of oral contraceptives, anti-androgen agents, insulin-sensitizing agents, and ovulation-inducing agents, and future treatment may consist of miRNA therapy, drug repositioning, and genetic markers that might be used for early identification and better management of ovarian dysfunction. Thus, the current review discusses ovarian dysfunction in PCOS, the involvement of potential genes and epigenetic factors, and miRNAs concerning ovulation and its therapeutic implications.