Effect of iodine excess exposure on thyroid development and differentiation through epigenetic mechanisms using embryonic stem cells and induced pluripotent stem cells

• Grant number: 15/16695-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 15, 2015
• End date: April 14, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Caroline Serrano Do Nascimento
• Supervisor: Pilar Santisteban
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Consejo Superior de Investigaciones Científicas (CSIC), Spain
• Associated to the scholarship: 12/24391-6 - Impact of iodine excess exposure during pregnancy and/or lactation on the hypothalamus-pituitary-thyroid axis activity in rat dams and their offspring, BP.PD

Abstract

Both iodine deficiency (ID) and excess (IE) impair thyroid hormones synthesis, causing serious consequences especially during fetal/neonatal periods. Our previous data indicated that pregnant rats exposed to IE induced hypothyroidism in the adult male rats offspring through epigenetic mechanisms. This study aims to investigate the effects of IE exposure on the development and differentiation of thyroid gland and the epigenetic mechanisms involved in this process. Mice embryos will be removed from the uteri of control or IE-treated (0.3 mg/L or 3 mg/L) pregnant mice. Moreover, murine iPS cells will be extracted from control mice and treated with IE (10-9-10-6 M NaI). Both murine iPS cells and endoderm explants dissected from 4-6 somites embryos will be differentiated into thyroid cells through the transfection of specific plasmids or treatment with specific morphogenesis or growth factors. Successful thyroid development will be evaluated in both conditions (C and IE) through the analysis of NIS, TSHR, Tg, TPO, PAX8, NKX2.1 and FOXE1 expression. Furthermore, the involvement of epigenetic mechanisms as DNA methylation and histones posttranslational modifications will be investigated. This project is original and innovative, and certainly will clarify the molecular basis involved in the IE effects on thyroid development. We consider that this study will enlarge the knowledge about the deleterious effects of iodine excess exposure and enable the implementation of intervention strategies.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SERRANO-NASCIMENTO, CAROLINE; MORILLO-BERNAL, JESUS; ROSA-RIBEIRO, RAFAELA; NUNES, MARIA TEREZA; SANTISTEBAN, PILAR. Impaired Gene Expression Due to Iodine Excess in the Development and Differentiation of Endoderm and Thyroid Is Associated with Epigenetic Changes. THYROID, v. 30, n. 4, JAN 2020. (13/05629-4, 12/24391-6, 16/18517-8, 15/16695-3)