Xerostomia in Pre- and Post-Menopause and Its Interface with Women's Oral Health: Development of an Organoid Model, Genetic and Epigenetic Analysiss

• Grant number: 25/03920-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2025
• End date: May 31, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Silvia Vanessa Lourenço
• Grantee: Cibele Pelissari dos Santos
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/12807-5 - Xerostomia in pre and post-menopause and its interface with women's oral health: investigation from bench to bedside, AP.TEM

Abstract

Menopause is one of the events associated with the aging of women, leading to numerous systemic and local consequences, including changes in oral health. Salivary gland hypofunction often results in xerostomia. It is known that alterations in this complex system arise not only from modifications in the glandular parenchyma but also from changes in the stroma and glandular microenvironment. Specifically, during menopause, there is progressive glandular senescence, with gradual replacement by adipose tissue, along with possible alterations in the supporting tissue, vascularization, and innervation, due to hypoestrogenism and the establishment of a chronic systemic inflammatory process characteristic of the post-menopausal phase. Currently, there is no specific treatment for xerostomia, but regenerative therapies using stem cells and tissue engineering show promising potential. We propose to establish primary populations of human and porcine salivary gland cells, utilizing monolayer techniques and 3D culture models to create organoids. These populations will be characterized for salivary gland phenotypic markers, including cytoskeletal markers, membrane proteins, and communication channels. Additionally, gene expression profiles and microRNAs identified in patient samples will be evaluated. Our proposal is to create in vitro organoid models of human and porcine salivary glands to conduct functional research on xerostomia. These models will reduce the need for large animal facilities and the use of a high number of laboratory animals, making them more comparable to human salivary glands. This approach will enable significant advances in understanding xerostomia and developing solutions for this condition.