Low Circulating Levels of miR-451a in Girls with Polycystic Ovary Syndrome: Different Effects of Randomized Treatments
Por:
Díaz-Silva M, Bassols J, López-Bermejo A, de Zegher F and Ibañez-Toda L
Publicada:
1 mar 2020
Ahead of Print:
15 nov 2019
Resumen:
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.
Filiaciones:
Díaz-Silva M:
Institut de Recerca Pediàtric Hospital Sant Joan de Déu, University of Barcelona, Esplugues, Barcelona, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain
Bassols J:
Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), Salt, Spain
López-Bermejo A:
Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI) and Dr. Josep Trueta Hospital, Girona, Spain
de Zegher F:
Department of Development & Regeneration, University of Leuven, Leuven, Belgium
Ibañez-Toda L:
Institut de Recerca Pediàtric Hospital Sant Joan de Déu, University of Barcelona, Esplugues, Barcelona, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain
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