Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article

Polycystic ovary syndrome (PCOS) is a common infertility disorder affecting a significant proportion of the global population. It is the main cause of anovulatory infertility in women and is the most common endocrinopathy affecting reproductive-aged women, with a prevalence of 8–13% depending on the criteria used and population studied. The disease is multifactorial and complex and, therefore, often difficult to diagnose due to overlapping symptoms. Multiple etiological factors have been implicated in PCOS. Due to the complex pathophysiology involving multiple pathways and proteins, single genetic diagnostic tests cannot be determined. Progress has been achieved in the management and diagnosis of PCOS; however, not much is known about the molecular players and signaling pathways underlying it. Conclusively PCOS is a polygenic and multifactorial syndromic disorder. Many genes have been associated with PCOS, which affect fertility either directly or indirectly. However, studies conducted on PCOS patients from multiple families failed to find a fully penetrant variant(s). The present study was designed to review the current genetic understanding of the disease. In the present review, we have discussed the clinical spectrum, the genetics, and the variants identified as being associated with PCOS. The mechanisms by which variants in the genes confer risk to PCOS and the nature of the physical and genetic interaction between the genetic elements underlying PCOS remain to be determined. Elucidation of genetic players and cellular pathways underlying PCOS will certainly increase our understanding of the pathophysiology of this syndrome. The study also discusses the current status of the treatment modalities for PCOS, which is important to find new ways of treatment.

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“…The impaired insulin level causes PCOS; thus, a mutation in calpain 10 also causes PCOS. Hence, CAPN10 is a candidate gene causing PCOS 109…”

Section: Variations Associated With Pcosmentioning

confidence: 99%

<p>Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives</p>

Khan

Ullah

Basit

2019

TACG

201

118

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“…PCOS affects between 5% and 15% of reproductive‐age women worldwide (Azziz, 2016) and is characterized by disrupted menses, metabolic dysfunction, and hormonal alterations. Critically, one of the primary hallmarks of the syndrome is the presence of “cysts,” or excess immature follicles, in the ovary (Ajmal, Khan, & Shaikh, 2019). Webber et al (2003) systematically profiled follicle populations in ovarian biopsies from healthy and PCOS patients, quantifying the abundance of immature follicles and finding a significant increase in primary follicles in ovaries from PCOS patients.…”

Section: Oocyte Attrition and Primordial Follicle Abundance Must Be Fmentioning

confidence: 99%

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

Grive

2020

Molecular Reproduction Devel

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The mammalian ovarian reserve is comprised of a finite pool of primordial follicles, representing the lifetime reproductive capacity of females. In most mammals, the reserve is produced during embryonic and early postnatal development with oocyte numbers peaking during mid‐to‐late gestation, and then experiencing a dramatic decline continuing until shortly after birth. Oocytes remaining after the bulk of this attrition are subsequently surrounded by a layer of somatic pre‐granulosa cells with these units then referred to as “primordial follicles.” The complex and varied cell death mechanisms intrinsic to this process are not only characteristic of, but also essential for, the proper formation of this pool of follicles, and as a result must be immaculately balanced to ensure long‐term fertility and reproductive health. Too few follicles can lead to Primary Ovarian Insufficiency, resulting in fertility loss and other features of aging, such as an overall shorter lifespan. On the other hand, whereas an excess of follicles might extend reproductive lifespan, this might also be the underlying etiology of other ovarian pathologies. The last decade, in particular, has vastly expanded our understanding of oocyte attrition and determinants of ovarian reserve abundance. By continuing to decipher the intricacies underlying the cell death processes and development of the initial primordial follicle pool, we may be in a much better position to understand idiopathic cases of premature follicle depletion and improve ovarian health in reproductive‐age women.

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“…The nature of PCOS is multifactorial and heterogeneous. Environmental factors such as prenatal androgen exposure, poor fetal growth, high carbohydrate consumption and acquired obesity interact with genetic origins and contribute to PCOS pathogenesis [ 5 , 6 , 7 , 8 , 9 ]. It is well established that insulin resistance (IR) and compensatory hyperinsulinaemia are central aetiological abnormalities in women with PCOS which lead to the overproduction of ovarian and adrenal androgens and an increase in androgen bioavailability through inhibition of sex hormone-binding globulin (SHBG) secretion [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in Metabolic Profile in the Women with a History of PCOS—A Long-Term Follow-Up Study

Jacewicz-Święcka

Kowalska

2020

JCM

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Data concerning metabolic consequences in women with polycystic ovary syndrome (PCOS) are delivered mainly by cross-sectional studies. In this research, we re-examined 31 Caucasian PCOS women after a median period of 120.9 months to evaluate the changes in metabolic syndrome components. Clinical examination, oral glucose tolerance test with estimations of glucose and insulin, lipids, sex hormone-binding globulin (SHBG) and sex hormones assessments were performed on two occasions. Additionally, the euglycaemic hyperinsulinaemic clamp technique was used at the baseline to assess insulin sensitivity (M-clamp value). In the end, the median age of participants was 35. We observed an increase in glucose concentrations, a decrease in insulin concentrations and no changes in insulin resistance markers. Final mean glucose, mean insulin, Matsuda index and body mass index (BMI) were correlated with baseline M-clamp value and SHBG (p < 0.01). During the follow-up, no one in the sample developed diabetes. The annualised incidence rate for conversion from normoglycaemia to prediabetes totalled 4.5%. Baseline BMI, free androgen index, fasting glucose and M-clamp value were identified as prediabetes predictors in young PCOS women (respectively, OR = 1.17, OR = 1.42, OR = 1.2, OR = 0.73, p < 0.05). Prediabetes appeared in 76.47% of the women with a final BMI of ≥ 25 kg/m2 and in 7.14% of the normal-weight women (p = 0.0001). In conclusion, we report a high rate of adverse change in glucose metabolism in overweight and obese participants, a deterioration in β-cell function and strong correlations between metabolic parameters assessed in the third and the fourth decade in PCOS women, emphasising the role of early intervention to prevent cardiometabolic diseases.

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Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article

Cited by 139 publications

References 32 publications

<p>Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives</p>

<p>Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives</p>

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

Changes in Metabolic Profile in the Women with a History of PCOS—A Long-Term Follow-Up Study

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