Micrornas related to polycystic ovary syndrome: a scientific review

Fatemeh Moradi,1 Behnaz enjezab,2 Akram ghadiri-anari,3,*

1. Student Research Committee, Shahid Sadoughi University of Medical Science
2. Research Center for Nursing and Midwifery Care ,Nursing and Midwifery School, Department of Midwifery, Shahid Sadoughi University of Medical Science
3. Diabetes Research Center, Shahid Sadoughi University of Medical Sciences

Abstract

Introduction

Polycystic ovary syndrome (pcos) is a multifactorial disorder with various genetic, metabolic, endocrine and environmental abnormalities with an estimated prevalence of 8–18% depending on diagnostic criteria. the characteristics of pcos include polycystic ovaries, hyperandrogenism, irregular menstrual cycles, and metabolic abnormalities such as hyperinsulinemia and obesity. there is increasing evidence suggesting that pcos affects the whole life of a woman, can begin in utero in genetically predisposed subjects, it manifests clinically at puberty, continues during the reproductive years. in recent years, micrornas (mirnas) have emerged as important regulators of gene expression involved in various cellular functions related to metabolism, inflammation, and reproduction. altered mirna expression has been associated with various diseases such as diabetes, insulin resistance, inflammation, and cancer. several mirnas have been identified in pcos. the aim of this study was review of micrornas related to polycystic ovary syndrome.

Methods

For this purpose,55 initial articles obtained and finally 27 articles from 2014 to 2018 were reviewed with the keywords of polycystic ovary syndrome, micrornas and epigenetics in pubmed, google scholar, wiley online library, springer link and elsevier.

Results

in the majority of studies, kind of method was descriptive- cross-sectional study, 5 study was interventional- in vivo and in vitro and one of them was review study. all papers had described different micrornas in pcos, that according to, reduced levels and discordance between the expressions of mir-23a/b were observed in the women with pcos and mir-23a/b were affected from testosterone and bmi, reversely. the expression of mir-93/25 is related to pcos and insulin resistance. free testosterone and free androgen index were positively correlated with expression of mir-93 and mir-21. specific follicular fluid mirnas are associated with phenotypical traits of pcos. the mir-518f-3p was differentially expressed in hyperandrogenic pcos patients andmir-224 differentially expressed in follicular fluid too. new data provided evidence for a functional role of mir-27a-3p in the gcs dysfunction that occurs in patients with pcos. the mir-146a rs2910164 and mir-222 rs2858060 polymorphisms are associated with an increased risk of pcos. the mir-16 promoted ovarian gcs proliferation and inhibited apoptosis through directly targeting pdcd4 in pcos. the expression of mir-9, mir-18b, mir-30c, mir-135a, mir-146a and mir-222 were significantly increased in pcos patients and the expression of mir-19b, mir-93 and mir-132 were significantly decreased in blastocysts of pcos patients. the expression of mir-27b and mir-103 and circulating mirna-93 and mirna-223, mir-21 expression in whole blood and serum expression of mir-155 were higher and decreased levels of mir-24-3p, -29a, -151-3p, and -574-3p was seen in pcos patients. themir-93 and serum mirna-6767-5p may be a novel candidate as a molecular biomarker in the diagnosis of pcos. the mirnas mir-92a, mir-92b, mir-145 and mir-182 may be involved in the pathogenesis of pcos. overexpression of mir‑19b may be a potential therapeutic approach for pcos. in addition, expression of mir-324-3p in the ovary of pcos rats was decreased significantly andmir‑33b‑5p was overexpressed in the ovarian tissues of insulin resistant pcos rats, and thus may play an important role in the development of insulin resistance in pcos patients.

Conclusion

Several mirnas have been identified in pcos. our understanding of mirnas, particularly in relation to pcos, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome. studies have shown that circulating mirnas are present in whole blood, serum, plasma and the follicular fluid of pcos patients and that these might serve as potential biomarkers and a new approach for the diagnosis of pcos.

Keywords

Polycystic ovary syndrome, micrornas, epigenetics