Analysis of the influence of miRNAs in the undervirilization of 46,XY patients with DSD and undetermined diagnosis

Abstract

Disorders of Sexual Development (DSD) affect 1: 1000-4500 live births and are defined as changes in which chromosomal, gonadal or genital development are atypical. Patients with DSD 46, XY have a broad phenotypic spectrum and many have atypical genitalia at birth. The diagnostic evaluation of a patient with DSD includes hormonal dosages, radiological, cytogenetic and molecular studies. However, a significant percentage of patients remain without etiology and have an indeterminate diagnosis. To better evaluate these cases, this project proposes to study the expression profile of experimentally validated miRNAs, which regulate the Androgen Receptor. The miRNAs are small non coding RNAs, which bind the 3'UTR region of mRNA targets, blocking protein synthesis. For example, it has been reported in the literature that the differential expression of miR-200c has been validated in genital tissue samples from hypospadic rats and in cell line derived from this tissue, suggesting the influence of miRNAs in the development of this genital abnormality, in these animals. In this project, ten patients with DSD 46, XY with undetermined diagnosis, that are being followed up at the Endocrinology Clinic of the Hospital das Clínicas (HC-FMUSP) and will undergo genitoplasty surgery, will be selected. The control group consists of individuals 46, XY of different age groups (n = 15), who will undergo postectomy surgery and who do not present other genito-urinary abnormalities. This original study will allow the evaluation of a possible role of miRNAs in the process of genital subvirilization in DSD 46, XY patients with undetermined diagnosis.