Investigating new processes in gonadal development

• Grant number: 24/00196-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2025
• End date: April 30, 2030
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Helena Fabbri Scallet
• Grantee: Helena Fabbri Scallet
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Benilton de Sá Carvalho ; Gil Guerra Júnior ; Olaf Hiort
• Associated scholarship(s): 25/07847-6 - INVESTIGATING NEW PROCESSES IN GONADAL DEVELOPMENT, BP.JP; 25/10332-8 - Genomics applied to the diagnosis of patients with Syndromic Disorders of Sexual Development, BP.MS; 25/08316-4 - in vitro evaluation of genetic variants and spatial transcriptomics of gonadal cells in patients with disorders of sex development, BP.DD

Abstract

Sexual development occurs through the activation of genes expressed on the sex chromosomes that lead to the formation of ovary or testicle from a bipotent gonad. This plasticity observed in the bipotent gonad, enabling its differentiation into two functionally distinct organs, represents a vast field of study that can be explored through various approaches. Gonadal differentiation is a complex process involving the precise expression of numerous genes and biological pathways. Disruptions in this process can result in conditions such as Disorders/Differences of Sex Development (DSDs), gonadoblastoma/dysgerminoma, and male infertility. DSD are congenital conditions characterized by a mismatch between the genetic, gonadal, and phenotypic sex of the affected individual, with significant variability in sexual phenotypes. his project aims to investigate the underlying causes of this variability through multi-omics analyses, integrating techniques such as transcriptomics, genomics and epigenomics. Additionally, to reassess the necessity of prophylactic gonadectomies in these patients, we will evaluate the potential malignancy of gonadal tissues using tumor markers. This will include identifying differentially expressed genes and conducting immunohistochemistry and/or immunofluorescence assays. Another aspect of this project involves evaluating the integrity of the blood-testis barrier in individuals undergoing treatment with gonadotropin analogs, with a focus on preserving long-term fertility. This will be accomplished through cellular localization assays and the analysis of proteins specific to this barrier. Through this project, we aim to establish a pipeline for omics analyses of rare diseases in our laboratory and expand our understanding of the mechanisms underlying gonadal development and associated conditions. This work has the potential to offer new insights into the complexity of sexual development pathways while supporting the establishment of a new research group within our institution. (AU)