Evaluation of circulating miRNAs profile in patients with polycystic ovary syndrome

Author(s)

Giovana De Nardo Maffazioli

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2021-04-29

Examining board members

Gustavo Arantes Rosa Maciel; Mariangela Badalotti; Edmund Chada Baracat; Marisa Passarelli

• Advisor: Gustavo Arantes Rosa Maciel; Kátia Cândido Carvalho

Abstract

Polycystic Ovary Syndrome (PCOS) is a complex and heterogeneous endocrinopathy characterized by chronic anovulation and Hyperandrogenism. It affects from 5 to 17% of reproductive aged women, and presents reproductive and metabolic dysfunctions associated to obesity, infertility and insulin resistance. The etiology of PCOS is still poorly understood, but it is known that it is related to a complex genetic trait associated with epigenetic factors. miRNAs are small non-coding molecules involved in the regulation of many body functions. These molecules were found in a variety of organs and body fluids. In the serum, they circulate inside small vesicles or free, and are relative stable and easily detected. Therefore, they are raising attention not only as potential biomarkers, but also as disease regulatory molecules. The aim of this study is to evaluate the expression profile of 201 circulating miRNA associated to PCOS, as well as insulin and glucose metabolic dysfunctions in a population of 36 PCOS women and 16 healthy controls. Clinical, anthropometric, hormonal and metabolic data were recorded and evaluated. The expression profile of the 201 circulating miRNAs selected were analyzed by quantitative real time polymerase chain reactions (qRT-PCR) using the Open Array platform. miRNAs that have shown to be the most promise were validated by the use of individual Taqman assays through qRT-PCR. Statistical and bioinformatics analyzes were performed. PCOS and control groups were matched by age (p=0.16) and ethnicity (p=0.87). As expected, PCOS group presented higher body mass index (BMI) (p=0.03), waist circumference (p=0.001), hirsutismo score (p=0.0001), hyperandrogenemia (p=0,02) and worse metabolic profile when comparing to the control group. From the 201 miRNAs selected, 95 presented enough expression to proceed with the analyzes. From these, 14 presented both significant foldregulation and relative expression. between the two groups. From these, 7 miRNAs were selected, based on the quantity of samples they were expressed, to procced to the validation step. After this, the miR-21-5p presented as the most promising miRNA in our sample and were analyzed along with clinical data. This miRNA had 81% chance of discriminating the PCOS group from control group, it was similar with the chance presented by the anti-mullerian hormone (AMH), widely studied as a promising biomarker of PCOS. Furthermore, this difference of expression seemed to be related to hyperandrogenism and triglycerides/HDLC rate, even though the mechanisms related to these association were not elucidated. miR-21-5p showed high potential of clinical applicability in the PCOS diagnosis. This study, thus, may contribute to a more rational and objective use of biomarkers that may be used in PCOS diagnosis, as well as in the prediction of its metabolic and reproductive disfunctions (AU)

• FAPESP's process: 16/23253-0 - Assessment of microRNAs and metabolites plasma profiles in patients with Polycystic Ovary Syndrome
• Grantee: Giovana de Nardo Maffazioli
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)