Identifying the molecular mechanisms underlying Gestational Hypothyroidism and Type 2 Diabetes susceptibility by constructing a 3D human placental barrier model

• Grant number: 19/09492-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2019
• Effective date (End): August 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Celia Regina Nogueira
• Grantee: Bianca Mariani Gonçalves Meneghim
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Thyroid Hormone (TH) accomplishes a crucial role in thorough placental and fetal development. However, transplacental transport of HT involves the integration between many mechanisms that have not been fully elucidated. Increasingly, researchers have been described the importance of the intrauterine environment and the involvement of mild maternal thyroid abnormalities with epigenetic failures, which could confer susceptibility to metabolic disorders in adulthood. One of the supposed mechanisms includes the reduced expression of deiodinase 3, a selenoenzyme controlled by epigenetic factors, with the occurrence of glucose intolerance in DM2. Deiodinase 3 has its main activity during the embryonic period, being responsible for managing the fetal thyroid demand. Nevertheless, its expression leads to the adult pancreatic beta-cell. We hypothesize that Gestational Hypothyroidism may lead to impaired local thyroid control, altering the metabolic, molecular, and epigenetic profiles related to pancreatic embryogenesis, conferring susceptibility to the development of DM2 in adult life. Thus, this study aims to evaluate the maternal-fetal-thyroid-pancreas interaction through the construction of a human placental organoid submitted to treatment with several doses of T3, T4, and rT3 in a co-culture system through pancreatic lineages. Subsequently, molecular analyses of gene expression profiling and microRNA will be performed to suggesting a possible relationship. (AU)