Comprehensive analysis of maternal and fetal epigenetic changes during perinatal period

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09707
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: miyasaka naoyuki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70313252)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: DOHaD / エピゲノム / 注意欠陥多動性障害 / 白血球組成 / マイクロRNA / 慢性疾患

Outline of Final Research Achievements

We have studied the maternal and fetal epigenetic changes during pregnancy using peripheral blood samples, and their association with the maternal environmental factors. Maternal epigenetic changes in lipid metabolism genes (CPT1A and SREBF1) during mid-gestation was similar to those reported in obese women. On the other hand, dynamic changes in methylation levels during pregnancy was affected by not only these metabolic changes but also differences in peripheral leukocyte population. Methylation in attention deficit hyperactivity disorder (ADHD) associated gene (SKI) in cord blood was correlated with protein/energy ratio of the dietary intake in early pregnancy. This finding might be useful for the prevention of ADHD. Finally, circulating exosomal micro RNA level was associated with fetal/placental weight ratio, which indicated that micro RNA might be a biomarker of feto-placental function and fetal growth.

Free Research Field

周産期医学

Academic Significance and Societal Importance of the Research Achievements

妊娠中の母体環境が胎児の遺伝子発現調節を修飾し、将来の慢性疾患の要因となること（Developmental Origin of Health and Disease, DOHaD）が注目されている。本研究では、妊娠中の母体栄養摂取や精神状態などの環境因子、母体血、臍帯血のエピゲノム関連因子を測定し、そのメカニズムを検討した。妊娠中の脂質代謝は肥満のそれと類似しているが、代謝変化以外にも細胞組成の影響を受けること、妊娠初期に母体が摂取したたんぱく質エネルギー比が注意欠陥多動性障害関連遺伝子に影響すること、母体血中の循環しているマイクロRNAが胎児胎盤機能の指標となることなどを明らかにした。