Epigenetic analysis of gene expression in central nervous system of offspring derived from dam with hypothyroxinemia during pregnancy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hashimoto Koshi 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (30396642)
• Co-Investigator(Renkei-kenkyūsha): OGAWA Yoshihiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70291424) ; KAMEI Yasutomi 京都府立大学, 生命環境科学研究科, 教授 (70300829)
• Research Collaborator: KAWAHORI Kenichi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 甲状腺機能低下 / 妊娠期 / BDNF / 海馬 / 学習・認知能力低下 / 水迷路試験 / DNAメチル化 / DOHaD

Outline of Final Research Achievements

Experimental rodents have shown that maternal hypothyroxinemia during pregnancy may adversely affect neurodevelopment in offspring, resulting in irreversible cognitive deficits. This could be due to persistent reduced expression of hippocampal brain derived neurotrophic factor gene (Bdnf), which plays a crucial role in the central nervous system (CNS) development. However, the underlying molecular mechanism remains unclear. In the current study, we showed that mild maternal hypothyroxinemia during pregnancy induced impaired learning capacity of mouse offspring in adulthood. We also demonstrated that prolonged reduction in hippocampal Bdnf expression of the offspring in according to persistent DNA hypermethylation in the promoter region of Bdnf exon Ⅳ. Thus, we provide the first evidence that mild maternal hypothyroixinemia induces persistent DNA hypermethylation in Bdnf in the offspring, which could confer long-term cognitive disorder.

Free Research Field

内分泌学