Study of the MicroRNA Expression Profile in Gonads of Patients with 46,XX Ovotesticular Difference of Sexual Development.

• Grant number: 25/05439-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: May 31, 2029
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sorahia Domenice
• Grantee: Laura da Silva Salvanini
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/26780-9 - Molecular and epigenetic research on Differences in Sexual Development (DSD): impact of scientific diffusion on the relationship between science and society, AP.TEM

Abstract

Gonadal determination in mammals is regulated by a complex network of genes, whose interactions dictate the formation of ovaries or testes, depending on the activation of female or male genetic pathways, respectively. Disruptions in this gene cascade can result in structural and functional alterations in the gonads, leading to a divergence between genetic and phenotypic sexes. Differences of Sex Development (DSD) encompass congenital conditions that may arise from such disruptions, with 46,XX ovotesticular DSD (OT-DSD) being among the most complex. This condition is characterized by the simultaneous presence of ovarian and testicular tissue, either within a single gonad (ovotestis) or as distinct gonads, and has been associated with mutations in genes involved in the gonadal determination pathway. However, for many patients, the etiological diagnosis remains undefined, underscoring the need to investigate additional regulatory pathways. MicroRNAs (miRNAs) are small transcripts that regulate gene expression post-transcriptionally by interacting with messenger RNA and have been implicated in controlling genes within the gonadal determination cascade. During gonadal organogenesis, specific miRNAs exhibit differential expression between XX and XY gonads, emphasizing their crucial role as fine-tuners of the pathways governing ovarian and testicular differentiation. Dysregulation of miRNA-mediated pathways may play a key role in disrupting the pro-ovarian genetic cascade in cases of 46,XX ovotesticular DSD (OT-DSD). This project aims to investigate the miRNA expression profile in ovarian and testicular tissues from 15 patients with 46,XX OT-DSD, treated at the Hospital das Clínicas, School of Medicine, University of São Paulo, using Next-Generation Sequencing (NGS). The findings will provide novel insights into the etiology of this condition and enhance the understanding of the role of miRNAs in gonadal determination, contributing to improved diagnosis and management of patients with this rare condition.