Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microR...

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Main Authors: Anja E. Sørensen, Pernille B. Udesen, Grzegorz Maciag, Julian Geiger, Negar Saliani, Andrzej S. Januszewski, Guozhi Jiang, Ronald C. Ma, Anandwardhan A. Hardikar, Marie Louise M. Wissing, Anne Lis M. Englund, Louise T. Dalgaard
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/article/10.3389/fmed.2019.00242/full
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author Anja E. Sørensen
Anja E. Sørensen
Pernille B. Udesen
Pernille B. Udesen
Grzegorz Maciag
Julian Geiger
Negar Saliani
Andrzej S. Januszewski
Guozhi Jiang
Ronald C. Ma
Anandwardhan A. Hardikar
Marie Louise M. Wissing
Anne Lis M. Englund
Louise T. Dalgaard
author_facet Anja E. Sørensen
Anja E. Sørensen
Pernille B. Udesen
Pernille B. Udesen
Grzegorz Maciag
Julian Geiger
Negar Saliani
Andrzej S. Januszewski
Guozhi Jiang
Ronald C. Ma
Anandwardhan A. Hardikar
Marie Louise M. Wissing
Anne Lis M. Englund
Louise T. Dalgaard
author_sort Anja E. Sørensen
collection DOAJ
description Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.
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spelling doaj.art-e72b4329758d40d785025cd4e3ae5a132022-12-21T23:56:41ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2019-11-01610.3389/fmed.2019.00242481229Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary SyndromeAnja E. Sørensen0Anja E. Sørensen1Pernille B. Udesen2Pernille B. Udesen3Grzegorz Maciag4Julian Geiger5Negar Saliani6Andrzej S. Januszewski7Guozhi Jiang8Ronald C. Ma9Anandwardhan A. Hardikar10Marie Louise M. Wissing11Anne Lis M. Englund12Louise T. Dalgaard13Department of Science and Environment, Roskilde University, Roskilde, DenmarkOdense University Hospital, The Danish Diabetes Academy, Odense, DenmarkDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkFertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Køge, DenmarkDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkDiabetes and Islet Biology Group, NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, AustraliaDepartment of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong KongDepartment of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong KongDiabetes and Islet Biology Group, NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, AustraliaFertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Køge, DenmarkFertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Køge, DenmarkDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkPolycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.https://www.frontiersin.org/article/10.3389/fmed.2019.00242/fullmicroRNApolycystic ovary syndromeserum free testosteronehyperandrogenismmetabolic syndromeTaqMan low density arrays
spellingShingle Anja E. Sørensen
Anja E. Sørensen
Pernille B. Udesen
Pernille B. Udesen
Grzegorz Maciag
Julian Geiger
Negar Saliani
Andrzej S. Januszewski
Guozhi Jiang
Ronald C. Ma
Anandwardhan A. Hardikar
Marie Louise M. Wissing
Anne Lis M. Englund
Louise T. Dalgaard
Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome
Frontiers in Medicine
microRNA
polycystic ovary syndrome
serum free testosterone
hyperandrogenism
metabolic syndrome
TaqMan low density arrays
title Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome
title_full Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome
title_fullStr Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome
title_full_unstemmed Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome
title_short Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome
title_sort hyperandrogenism and metabolic syndrome are associated with changes in serum derived micrornas in women with polycystic ovary syndrome
topic microRNA
polycystic ovary syndrome
serum free testosterone
hyperandrogenism
metabolic syndrome
TaqMan low density arrays
url https://www.frontiersin.org/article/10.3389/fmed.2019.00242/full
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