Low circulating levels of miR-451a in girls with Polycystic Ovary Syndrome: different effects of randomized treatments
Ibanez, Lourdes et al. (2020), Low circulating levels of miR-451a in girls with Polycystic Ovary Syndrome: different effects of randomized treatments, Dryad, Dataset, https://doi.org/10.5061/dryad.9cnp5hqdn
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 miRNA profile of girls with PCOS, and the effects of a randomized treatment with an oral contraceptive (OC) or with spironolactone-pioglitazone-metformin (SPIOMET, aiming at loss of hepato-visceral fat excess) for 1 year.
Design & Patients:The miRNA profile was assessed by RNA sequencingin girls with PCOS who had participated in a randomized, open-label, single-center, pilot study (n=31; age 15.7 years, BMI 23.1 Kg/m2). Healthy age- and BMI-matched girls (n=13) served as controls. Differentially expressedmiRNAs were validated by qRT-PCR 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 -as compared to 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<0.0001) 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.
This is a first pilot, proof-of-concept study wherein the miRNA profile of adolescent girls with PCOS was compared to that of healthy control girls, and wherein the effects of a randomized intervention with two different medications (for 1 year) on the miRNA profile were compared.
Instituto de Salud Carlos III, and by the Fondo Europeo de Desarrollo Regional (FEDER), Award: PI15/01078