Low Circulating Levels of miR-451a in Girls with Polycystic Ovary Syndrome: Different Effects of Randomized Treatments

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder in adolescent girls, purportedly driven by hepato-visceral fat excess, and often followed by subfertility and type 2 diabetes. Objective: We studied the baseline microRNA (miRNA) profile of girls with PCOS, and the effects of a random...

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Detalles Bibliográficos
Autores: Díaz M, Bassols J, López-Bermejo A, de Zegher F, Ibáñez L
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p16858
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=16858
Access Level:acceso abierto
Palabra clave:PCOS
miRNAs
hepato-visceral fat
metformin
spironolactone
pioglitazone
Descripción
Sumario:Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder in adolescent girls, purportedly driven by hepato-visceral fat excess, and often followed by subfertility and type 2 diabetes. Objective: We studied the baseline microRNA (miRNA) profile of girls with PCOS, and the effects of a randomized treatment with an oral contraceptive (OC) or with spironolactonepioglitazone-metformin (SPIOMET, aiming at loss of hepato-visceral fat excess) for 1 year. Design & Patients: The miRNA profile was assessed by RNA sequencing in girls with PCOS who had participated in a randomized, open-label, single-center, pilot study (n = 31; age 15.7 years, body mass index (BMI) 23.1 kg/m(2)). Healthy age- and BMI-matched girls (n = 13) served as controls. Differentially expressed miRNAs were validated by RT-qPCR in the entire study population. Post-treatment ovulation rates were assessed by salivary progesterone in PCOS girls. Setting: Endocrinology Department, University Hospital. Results: Girls with PCOS, compared with controls, had markedly reduced concentrations of circulating miR-451a, miR-652-3p, miR-106b-5p, and miR-206; pathway enrichment analysis showed that these miRNAs target genes involved in energy homeostasis and cell cycle control. In the present study, miR-451a could diagnose PCOS with 100% sensitivity and 100% specificity. SPIOMET (but not OC) was accompanied by on-treatment normalization of the miRNA profile in girls with PCOS; miR-451a concentrations after 1 year on OC or SPIOMET treatment associated closely (r = 0.66; P <.0001) with post-treatment ovulation rates. Conclusion: SPIOMET treatment for 1 year normalizes the miRNA profile of girls with PCOS. Circulating miR-451a may become a biomarker to guide the diagnosis and treatment of PCOS in adolescence.