DIFERENTIATION OF GONADAL CELLS FROM iPSCs TO STUDY DIFFERENCES OF SEXUAL DEVELOPMENT

• Grant number: 24/23694-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: January 31, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Berenice Bilharinho de Mendonça
• Grantee: Juliana Moreira Silva
• 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

Differences in Sexual Development (DSD) represent a spectrum of genetic conditions characterized by altered gonadal development and sexual phenotype, often linked to unknown molecular etiologies. This project aims to establish and characterize an in vitro model to study normal human gonadal development and DSD conditions using induced pluripotent stem cells (iPSCs). The methodology involves differentiating iPSCs into bipotential and testis gonadal cells, following protocols mimicking human gonadal embryogenesis. The DHX37 gene, recently associated with 46,XY DSD, will be investigated for its expression and role during gonadal differentiation and disease pathogenesis. Patients with DSD, monitored in specialized centers and carrying pathogenic variants in DHX37, will have iPSCs derived from peripheral blood mononuclear cells. These cells will be differentiated and compared to healthy controls for morphological, transcriptional, and functional markers. Expected outcomes include establishing a robust cellular model to elucidate the molecular and cellular mechanisms underlying gonadal development, identifying critical signaling pathways, and providing a platform to validate future therapeutic approaches. This study has the potential to advance the understanding of DSD and improve diagnosis and treatment of these conditions.