Impaired Gene Expression Due to Iodine Excess in the Development and Differentiation of Endoderm and Thyroid Is Associated with Epigenetic Changes

Author(s)

Serrano-Nascimento, Caroline ^{[1, 2, 3, 4]} ; Morillo-Bernal, Jesus ^{[3, 4]} ; Rosa-Ribeiro, Rafaela ^[2] ; Nunes, Maria Tereza ^[1] ; Santisteban, Pilar ^{[3, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Hosp Israelita Albert Einstein, Inst Ensino & Pesquisa, Sao Paulo - Brazil

^[3] CSIC UAM, Inst Invest Biomed Alberto Sols, Madrid - Spain

^[4] CIBERONC Inst Salud Carlos III, Madrid - Spain

• Document type: Journal article
• Source: THYROID; v. 30, n. 4 JAN 2020.
• Web of Science Citations: 0

Abstract

Background: Thyroid hormone (TH) synthesis is essential for the control of development, growth, and metabolism in vertebrates and depends on a sufficient dietary iodine intake. Importantly, both iodine deficiency and iodine excess (IE) impair TH synthesis, causing serious health problems especially during fetal/neonatal development. While it is known that IE disrupts thyroid function by inhibiting thyroid gene expression, its effects on thyroid development are less clear. Accordingly, this study sought to investigate the effects of IE during the embryonic development/differentiation of endoderm and the thyroid gland. Methods: We used the murine embryonic stem (ES) cell model of in vitro directed differentiation to assess the impact of IE on the generation of endoderm and thyroid cells. Additionally, we subjected endoderm and thyroid explants obtained during early gestation to IE and evaluated gene and protein expression of endodermal markers in both models. Results: ES cells were successfully differentiated into endoderm cells and, subsequently, into thyrocytes expressing the specific thyroid markers Tshr, Slc5a5, Tpo, and Tg. IE exposure decreased the messenger RNA (mRNA) levels of the main endoderm markers Afp, Crcx4, Foxa1, Foxa2, and Sox17 in both ES cell-derived endoderm cells and embryonic explants. Interestingly, IE also decreased the expression of the main thyroid markers in ES cell-derived thyrocytes and thyroid explants. Finally, we demonstrate that DNA methyltransferase expression was increased by exposure to IE, and this was accompanied by hypermethylation and hypoacetylation of histone H3, pointing to an association between the gene repression triggered by IE and the observed epigenetic changes. Conclusions: These data establish that IE treatment is deleterious for embryonic endoderm and thyroid gene expression. (AU)

• FAPESP's process: 13/05629-4 - Genomic vs nongenomic actions of thyroid hormones: changes of paradigms, physiological implications and therapeutical perspectives
• Grantee: Maria Tereza Nunes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 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
• Grantee: Caroline Serrano Do Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/18517-8 - Endocrine disruptors vs. thyroid: an epigenetic analysis of the development, differentiation and function of thyrocytes and their repercussions on the organism
• Grantee: Caroline Serrano Do Nascimento
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/16695-3 - Effect of iodine excess exposure on thyroid development and differentiation through epigenetic mechanisms using embryonic stem cells and induced pluripotent stem cells
• Grantee: Caroline Serrano Do Nascimento
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor