Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study
Background: Women with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of...
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MDPI AG
2023-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/983 |
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| author | Pernille B. Udesen Anja E. Sørensen Rikke Svendsen Nanna L. S. Frisk Anne L. Hess Mubeena Aziz Marie Louise M. Wissing Anne Lis M. Englund Louise T. Dalgaard |
| author_facet | Pernille B. Udesen Anja E. Sørensen Rikke Svendsen Nanna L. S. Frisk Anne L. Hess Mubeena Aziz Marie Louise M. Wissing Anne Lis M. Englund Louise T. Dalgaard |
| author_sort | Pernille B. Udesen |
| collection | DOAJ |
| description | Background: Women with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS. Methods and materials: Clinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman<sup>®</sup> Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease. Results: Women with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, p<sub>adj</sub> = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, p<sub>adj</sub> = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling. Conclusions: These studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile. |
| first_indexed | 2024-03-11T05:41:27Z |
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| id | doaj.art-f56ac2d15f0843078d8c208e1acad3e4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:41:27Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-f56ac2d15f0843078d8c208e1acad3e42023-11-17T16:27:37ZengMDPI AGCells2073-44092023-03-0112798310.3390/cells12070983Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort StudyPernille B. Udesen0Anja E. Sørensen1Rikke Svendsen2Nanna L. S. Frisk3Anne L. Hess4Mubeena Aziz5Marie Louise M. Wissing6Anne Lis M. Englund7Louise T. Dalgaard8Fertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Lykkebækvej 14, 4600 Koege, DenmarkDepartment of Science and Environment, Universitetsvej 1, 4000 Roskilde, DenmarkDepartment of Science and Environment, Universitetsvej 1, 4000 Roskilde, DenmarkDepartment of Science and Environment, Universitetsvej 1, 4000 Roskilde, DenmarkDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, DenmarkDepartment of Gynecology and Obstetrics, Amager/Hvidovre Hospital, Kettegaards Allé 30, 2650 Hvidovre, DenmarkDepartment of Science and Environment, Universitetsvej 1, 4000 Roskilde, DenmarkFertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Lykkebækvej 14, 4600 Koege, DenmarkDepartment of Science and Environment, Universitetsvej 1, 4000 Roskilde, DenmarkBackground: Women with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS. Methods and materials: Clinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman<sup>®</sup> Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease. Results: Women with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, p<sub>adj</sub> = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, p<sub>adj</sub> = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling. Conclusions: These studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile.https://www.mdpi.com/2073-4409/12/7/983biomarkermetabolic syndromemicroRNAPCOSpolycystic ovary syndromecirculation |
| spellingShingle | Pernille B. Udesen Anja E. Sørensen Rikke Svendsen Nanna L. S. Frisk Anne L. Hess Mubeena Aziz Marie Louise M. Wissing Anne Lis M. Englund Louise T. Dalgaard Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study Cells biomarker metabolic syndrome microRNA PCOS polycystic ovary syndrome circulation |
| title | Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study |
| title_full | Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study |
| title_fullStr | Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study |
| title_full_unstemmed | Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study |
| title_short | Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study |
| title_sort | circulating mirnas in women with polycystic ovary syndrome a longitudinal cohort study |
| topic | biomarker metabolic syndrome microRNA PCOS polycystic ovary syndrome circulation |
| url | https://www.mdpi.com/2073-4409/12/7/983 |
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