{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:24:04Z","timestamp":1782260644275,"version":"3.54.5"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ReproUnion and the Danish Diabetes Academy"},{"name":"Novo Nordisk Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u00ae 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, padj = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, padj = 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.<\/jats:p>","DOI":"10.3390\/cells12070983","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:31:05Z","timestamp":1679632265000},"page":"983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Pernille B.","family":"Udesen","sequence":"first","affiliation":[{"name":"Fertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Lykkeb\u00e6kvej 14, 4600 Koege, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja E.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Universitetsvej 1, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"Svendsen","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Universitetsvej 1, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna L. S.","family":"Frisk","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Universitetsvej 1, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne L.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubeena","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Amager\/Hvidovre Hospital, Kettegaards All\u00e9 30, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Louise M.","family":"Wissing","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Universitetsvej 1, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Lis M.","family":"Englund","sequence":"additional","affiliation":[{"name":"Fertility Clinic, Department of Gynecology and Obstetrics, Zealand University Hospital, Lykkeb\u00e6kvej 14, 4600 Koege, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3598-2775","authenticated-orcid":false,"given":"Louise T.","family":"Dalgaard","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Universitetsvej 1, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/cen.13795","article-title":"Pcos Network International. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"89","author":"Teede","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1210\/er.2011-1034","article-title":"Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanisms and implications","volume":"33","author":"Dunaif","year":"2012","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12933-018-0680-5","article-title":"Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome","volume":"17","author":"Glintborg","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1210\/jc.2017-01354","article-title":"Development and Risk Factors of Type 2 Diabetes in a Nationwide Population of Women with Polycystic Ovary Syndrome","volume":"102","author":"Rubin","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/apha.12681","article-title":"MicroRNAs in metabolism","volume":"219","author":"Vienberg","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.tem.2009.05.007","article-title":"Meta-regulation: microRNA regulation of glucose and lipid metabolism","volume":"20","author":"Lynn","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9514927","DOI":"10.1155\/2018\/9514927","article-title":"Circulating Noncoding RNAs as Candidate Biomarkers of Endocrine and Metabolic Diseases","volume":"2018","author":"Sebastiani","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/oby.22704","article-title":"Levels of Circulating miR-122 are Associated with Weight Loss and Metabolic Syndrome","volume":"28","author":"Hess","year":"2020","journal-title":"Obesity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.2337\/dc13-1847","article-title":"Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization","volume":"37","author":"Ortega","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/oby.22379","article-title":"Bariatric Surgery Alters microRNA Content of Circulating Exosomes in Patients with Obesity","volume":"27","author":"Bae","year":"2019","journal-title":"Obesity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2337\/db16-0731","article-title":"Circulating MicroRNA-122 Is Associated with the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes","volume":"66","author":"Willeit","year":"2017","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E2271","DOI":"10.1210\/jc.2012-1996","article-title":"Circulating miRNA profiles in patients with metabolic syndrome","volume":"97","author":"Karolina","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cbi.2016.06.008","article-title":"MicroRNAs related to androgen metabolism and polycystic ovary syndrome","volume":"259 Pt A","author":"Sorensen","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"684","DOI":"10.3390\/genes5030684","article-title":"MicroRNAs Related to Polycystic Ovary Syndrome (PCOS)","volume":"5","author":"Sorensen","year":"2014","journal-title":"Genes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.fertnstert.2016.10.003","article-title":"Elevated circulating micro-ribonucleic acid (miRNA)-200b and miRNA-429 levels in anovulatory women","volume":"107","author":"Eisenberg","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.metabol.2018.01.011","article-title":"San-Millan, J.L. Luque-Ramirez, M. Escobar-Morreale, H.F. Non-targeted profiling of circulating microRNAs in women with polycystic ovary syndrome (PCOS): Effects of obesity and sex hormones","volume":"86","author":"Murri","year":"2018","journal-title":"Metabolism"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E1835","DOI":"10.1210\/jc.2013-2218","article-title":"San-Millan, J.L. Escobar-Morreale, H.F. Effects of polycystic ovary syndrome (PCOS), sex hormones, and obesity on circulating miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 expression","volume":"98","author":"Murri","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12020-016-0878-9","article-title":"Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome","volume":"53","author":"Jiang","year":"2016","journal-title":"Endocrine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111723","DOI":"10.1016\/j.mce.2022.111723","article-title":"Srinouanprachanh, S.; Kaleru, T.; Khakpour, D.; Trikudanathan, S. Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome\u2014Pilot study","volume":"554","author":"Wander","year":"2022","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1210\/jc.2015-3588","article-title":"MicroRNA Species in Follicular Fluid Associating With Polycystic Ovary Syndrome and Related Intermediary Phenotypes","volume":"101","author":"Sorensen","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1210\/jc.2013-1715","article-title":"Identification of microRNAs in human follicular fluid: Characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo","volume":"98","author":"Sang","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E729","DOI":"10.1210\/jc.2014-3827","article-title":"MicroRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome","volume":"100","author":"Jiang","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.2337\/db12-0963","article-title":"miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of Polycystic Ovary Syndrome patients and women with insulin resistance","volume":"62","author":"Chen","year":"2013","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16890","DOI":"10.1038\/srep16890","article-title":"Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis","volume":"5","author":"Sathyapalan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14671","DOI":"10.1038\/s41598-017-13250-1","article-title":"Differential Expression of miR-93 and miR-21 in Granulosa Cells and Follicular Fluid of Polycystic Ovary Syndrome Associating with Different Phenotypes","volume":"7","author":"Naji","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.7754\/Clin.Lab.2015.150122","article-title":"Ciculating miRNA-21 as a Biomarker Predicts Polycystic Ovary Syndrome (PCOS) in Patients","volume":"61","author":"Jiang","year":"2015","journal-title":"Clin. Lab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vitale, S.G., Fulghesu, A.M., Mikus, M., Watrowski, R., D\u2019Alterio, M.N., Lin, L.T., Shah, M., Reyes-Munoz, E., Sathyapalan, T., and Angioni, S. (2022). The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside-A Systematic Literature Review. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081816"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.fertnstert.2011.09.024","article-title":"Consensus on women\u2019s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE\/ASRM-Sponsored 3rd PCOS Consensus Workshop Group","volume":"97","author":"Fauser","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3109\/09513590.2011.613966","article-title":"Polycystic ovary syndrome: Infertility, cardiovascular, metabolic and obstetrical risks, laboratory and clinical outcomes -- the PICOLO Study","volume":"28","author":"Aziz","year":"2012","journal-title":"Gynecol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.rbmo.2013.11.017","article-title":"Impact of PCOS on early embryo cleavage kinetics","volume":"28","author":"Wissing","year":"2013","journal-title":"Reprod. Biomed. Online"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3389\/fmed.2019.00242","article-title":"Dalgaard. Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome","volume":"6","author":"Sorensen","year":"2019","journal-title":"Front. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1210\/jcem.84.10.6079","article-title":"A critical evaluation of simple methods for the estimation of free testosterone in serum","volume":"84","author":"Vermeulen","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","unstructured":"Kolde, R. (2023, February 20). Pheatmap. (2019). Available online: https:\/\/cran.r-project.org\/package=pheatmap."},{"key":"ref_36","unstructured":"Wei, T., and Simko, V. (2023, February 20). R Package Corrplot: Visualization of a Correlation Matrix. (2017). Available online: https:\/\/github.com\/taiyun\/corrplot."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v098.i11","article-title":"Cutpointr: Improved Estimation and Validation of Optimal Cutpoints in R","volume":"98","author":"Thiele","year":"2021","journal-title":"J. Stat. Softw."},{"key":"ref_38","first-page":"165","article-title":"Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women","volume":"84","author":"Legro","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/cen.14647","article-title":"Natural history of polycystic ovary syndrome: A systematic review of cardiometabolic outcomes from longitudinal cohort studies","volume":"96","author":"Kiconco","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1210\/jc.2010-2959","article-title":"Reproductive Hormone Levels and Anthropometry in Postmenopausal Women with Polycystic Ovary Syndrome (PCOS): A 21-Year Follow-Up Study of Women Diagnosed with PCOS around 50 Years Ago and Their Age-Matched Controls","volume":"96","author":"Schmidt","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1210\/jc.2015-2123","article-title":"Androgen Profile Through Life in Women With Polycystic Ovary Syndrome: A Nordic Multicenter Collaboration Study","volume":"100","author":"Pinola","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8185","DOI":"10.1073\/pnas.1322466111","article-title":"MicroRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas","volume":"111","author":"Schneider","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, B., Zhao, H., Li, T., Gao, X., Gao, Q., Tang, R., Zhang, J., and Chen, Z.J. (2012). Association study of gene LPP in women with polycystic ovary syndrome. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046370"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.omtn.2018.05.002","article-title":"Delgado-Lista, J.; Castano, J.P.; et al. Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus Development in Coronary Heart Disease Patients from the CORDIOPREV Study","volume":"12","year":"2018","journal-title":"Mol. Ther. Nucleic. Acids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/CIRCRESAHA.110.226357","article-title":"Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes","volume":"107","author":"Zampetaki","year":"2010","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00404-016-4068-z","article-title":"Altered FoxO3 expression and apoptosis in granulosa cells of women with polycystic ovary syndrome","volume":"294","author":"Mikaeili","year":"2016","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3390\/genes5030508","article-title":"Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study","volume":"5","author":"Thuesen","year":"2014","journal-title":"Genes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 regulate insulin sensitivity","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1093\/abbs\/gmaa008","article-title":"Up-regulation of miR-139-5p protects diabetic mice from liver tissue damage and oxidative stress through inhibiting Notch signaling pathway","volume":"52","author":"Wei","year":"2020","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8737","DOI":"10.2147\/IJGM.S335108","article-title":"WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs","volume":"14","author":"Li","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1261\/rna.042143.113","article-title":"miR-139-5p is a regulator of metastatic pathways in breast cancer","volume":"19","author":"Krishnan","year":"2013","journal-title":"RNA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1038\/onc.2011.453","article-title":"Attenuation of the beta-catenin\/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes","volume":"31","author":"Schepeler","year":"2012","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.bbrc.2017.07.057","article-title":"Deregulation of WNT2\/FZD3\/beta-catenin pathway compromises the estrogen synthesis in cumulus cells from patients with polycystic ovary syndrome","volume":"493","author":"Qiao","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1210\/en.2019-00428","article-title":"Neuroendocrine Impairments of Polycystic Ovary Syndrome","volume":"160","author":"Ruddenklau","year":"2019","journal-title":"Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13048-014-0110-6","article-title":"The transcriptome of corona radiata cells from individual Mcapital I, Ukrainiancapital I, Ukrainian oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women","volume":"7","author":"Wissing","year":"2014","journal-title":"J. Ovarian. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"725","DOI":"10.18632\/aging.100603","article-title":"Age-related changes in microRNA levels in serum","volume":"5","author":"Hooten","year":"2013","journal-title":"Aging"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/gerona\/glu145","article-title":"Investigation of microRNA expression in human serum during the aging process","volume":"70","author":"Zhang","year":"2015","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/acel.12469","article-title":"Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence","volume":"15","author":"Hooten","year":"2016","journal-title":"Aging Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1530\/EC-20-0195","article-title":"Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome","volume":"9","author":"Udesen","year":"2020","journal-title":"Endocr. 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