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      MicroRNAs Related to Polycystic Ovary Syndrome (PCOS)

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          Abstract

          Polycystic ovary syndrome (PCOS) is the most common, though heterogeneous, endocrine aberration in women of reproductive age, with high prevalence and socioeconomic costs. The syndrome is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism, as well as being associated with infertility, insulin resistance, chronic low-grade inflammation and an increased life time risk of type 2 diabetes. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post-transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that they might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. 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.

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          Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

          Lee P. Lim, Nelson C. Lau, Philip Garrett-Engele … (2005)
          MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.
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            Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.

            Yoshimasa Saito, Gangning Liang, Gerda Egger … (2006)
            Expression profiling of T24 cells revealed that 17 out of 313 human miRNAs were upregulated more than 3-fold by simultaneous treatment with the chromatin-modifying drugs 5-aza-2'-deoxycytidine and 4-phenylbutyric acid. One of these, miR-127, is embedded in a CpG island and is highly induced from its own promoter after treatment. miR-127 is usually expressed as part of a miRNA cluster in normal cells but not in cancer cells, suggesting that it is subject to epigenetic silencing. In addition, the proto-oncogene BCL6, a potential target of miR-127, was translationally downregulated after treatment. These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors.
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              Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria.

              Zuhal Yapici, Hakan Yarali, Bulent Okan Yildiz … (2012)
              What is the prevalence, phenotype and metabolic features of polycystic ovary syndrome (PCOS) in the same population according to three different diagnostic criteria? The prevalence of PCOS under National Institutes of Health (NIH), Rotterdam and Androgen Excess and PCOS (AE-PCOS) Society criteria was 6.1, 19.9 and 15.3%, respectively. PCOS carried a 2-fold increased risk of metabolic syndrome regardless of the diagnostic criteria used. The prevalence rates of PCOS differ depending on the diagnostic criteria used to define the syndrome. The current paper gives the prevalence rates of the component and composite phenotypes of PCOS in the same population and reports similar rates of metabolic syndrome in women with PCOS under contrasting diagnostic criteria. In this cross-sectional study, 392 women between the ages of 18 and 45 years were analyzed. When the prevalence of PCOS according to NIH was set to 8% with a precision of 2.2% and confidence interval of 95%, the sample size required for a prevalence survey was found to be 400 subjects. The study was carried out in the General Directorate of Mineral Research and Exploration, a government-based institute, in which the largest number of female staff (n = 527) are employed within a single institute in Ankara, Turkey. The study was performed between 7 December 2009 and 30 April 2010. All female subjects between the ages of 18 and 45 years were invited to participate. Women older than 45 or younger than 18 years, post-menopausal women, women with a history of hysterectomy or bilateral oopherectomy and pregnant women were excluded. Totally, 392 of the employees were recruited for the final analyses. The prevalence of PCOS under NIH, Rotterdam and AE-PCOS Society criteria were 6.1, 19.9 and 15.3%, respectively. While the prevalence of metabolic syndrome was 6.1% in the whole study group, within the patients diagnosed as PCOS according to NIH, Rotterdam and AE-PCOS Society criteria, it was 12.5, 10.3 and 10.0%, respectively. Even though we have included women working at a single institution with a high response rate for the participation, we cannot exclude potential selection bias due to undetermined differences between our sample and background community. We might have underestimated actual prevalence of metabolic syndrome in PCOS due to lack of oral glucose tolerance test 2 h glucose data. Current results can be generalized to Caucasian populations and may present variations in other populations according to race and ethnicity. This work was, in part, sponsored by Merck Serono. Not applicable.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Genes (Basel)
                Journal ID (iso-abbrev): Genes (Basel)
                Journal ID (publisher-id): genes
                Title: Genes
                Publisher: MDPI
                ISSN (Electronic): 2073-4425
                Publication date (Electronic): 25 August 2014
                Publication date Collection: September 2014
                Volume: 5
                Issue: 3
                Pages: 684-708
                Affiliations
                [1 ]Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, Roskilde 4000, Denmark; E-Mails: sofias@ 123456ruc.dk (S.S.); ltd@ 123456ruc.dk (L.T.D.)
                [2 ]Fertility Clinic Region Sjaelland, Holbaek Hospital, Holbaek 4300, Denmark; E-Mails: mlwi@ 123456regionsjaelland.dk (M.L.W.); aleg@ 123456regionsjaelland.dk (A.L.M.E.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: elaine@ 123456ruc.dk ; Tel.: +45-4674-3994.
                Article
                Publisher ID: genes-05-00684
                DOI: 10.3390/genes5030684
                PMC ID: 4198925
                PubMed ID: 25158044
                SO-VID: 7685cfc0-76d0-423c-baab-ae1b458b55d2
                Copyright © © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 13 June 2014
                Date revision received : 07 August 2014
                Date accepted : 12 August 2014
                Categories
                Subject: Review

                Keywords: polycystic ovary syndrome,microrna,biomarkers,insulin resistance,infertility,diabetes
                Data availability:
                Keywords: polycystic ovary syndrome, microrna, biomarkers, insulin resistance, infertility, diabetes

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