Polycystic Ovarian Syndrome: A Complex Disease with a Genetics Approach

Abstract

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which supports the positive diagnosis of PCOS when patients present two out of the following three symptoms: biochemical and clinical signs of hyperandrogenism, oligo, and anovulation, also polycystic ovarian morphology on sonography. Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances, which include hyperandrogenism, insulin resistance, and chronic inflammation in PCOS females. At the molecular level, different proteins and molecular and signaling pathways are involved in disease progression, which leads to the failure of a single genetic diagnostic approach. The genetic approach to elucidate the mechanism of pathogenesis of PCOS was recently developed, whereby four phenotypic variances of PCOS categorize PCOS patients into classic, ovulatory, and non-hyperandrogenic types. Genetic studies help to identify the root cause for the development of this PCOS. PCOS genetic inheritance is autosomal dominant but the latest investigations revealed it as a multigene origin disease. Different genetic loci and specific genes have been identified so far as being associated with this disease. Genome-wide association studies (GWAS) and related genetic studies have changed the scenario for the diagnosis and treatment of this reproductive and metabolic condition known as PCOS. This review article briefly discusses different genes associated directly or indirectly with disease development and progression.

Keywords: biochemical; hyperandrogenism; multigene; ovulatory; polycystic.

Figure 1

Diagrammatic Representation of Polycystic Ovary Syndrome.

Figure 2

(a) Pathophysiologic features of polycystic ovary syndrome. PCOS is a multifactorial disorder that develops due to the combined effects of impaired genetic, epigenetic, and lifestyle factors. All these factors lead to disturbed pathophysiology (insulin resistance, hyperandrogenism, and low grade inflammation, which further result in complex symptoms of PCOS (Clinical, Reproductive, Metabolic, and Psychological). (b) Genetic influences and complications of polycystic ovarian syndrome. Different genetic polymorphism influences the pathophysiology of PCOS. Genetic influence alters different hormonal levels—androgen, insulin, AMH, SHBG, LH, FSH, testosterone, and different other hormonal levels, which further contribute to disease progression.

Figure 2

(a) Pathophysiologic features of polycystic ovary syndrome. PCOS is a multifactorial disorder that develops due to the combined effects of impaired genetic, epigenetic, and lifestyle factors. All these factors lead to disturbed pathophysiology (insulin resistance, hyperandrogenism, and low grade inflammation, which further result in complex symptoms of PCOS (Clinical, Reproductive, Metabolic, and Psychological). (b) Genetic influences and complications of polycystic ovarian syndrome. Different genetic polymorphism influences the pathophysiology of PCOS. Genetic influence alters different hormonal levels—androgen, insulin, AMH, SHBG, LH, FSH, testosterone, and different other hormonal levels, which further contribute to disease progression.