Study on epigenetic changes of the genes involved in the malformations of the fetus affected by diabetes

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09827
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kumamoto University
• Principal Investigator: Ohba Takashi 熊本大学, 大学院生命科学研究部(医), 准教授 (50244132)
• Co-Investigator(Kenkyū-buntansha): 副島 英伸 佐賀大学, 医学部, 教授 (30304885) ; 荒木 喜美 熊本大学, 生命資源研究・支援センター, 教授 (90211705)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 胎児異常 / 糖尿病合併妊娠 / エピゲノム変異 / 尾部退行症候群 / PTF1A

Outline of Final Research Achievements

We obtained written consent from the pregnant wmen whose HbA1c was evaluated in early pregnancy and the outcome of the mother and child could be studied at our institution including 12 patients with type 1 diabetes, 10 with type 2 diabetes, 13 with gestational diabetes mellitus, and 7 controls (HbA1c normal in early pregnancy and normal on glucose tolerance test during pregnancy). Cord blood and trophoblastic tissue samples were collected for DNA and RNA extraction. No newborns presented with caudal regression syndrome (CRS) or external genitalia abnormalities. Although there was a delay in the start of analysis due to the COVID-19, analysis of epigenomic mutations is now underway.

Free Research Field

産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

胎児形態異常は糖尿病合併妊娠における周産期死亡原因の約半数を占める。妊娠初期の高血糖が胎児形態異常の発生に関わることは明らかだがその機序は不明であった。我々は糖尿病合併妊娠に疾患特異的な稀少疾患である尾部退行症候群のモデルマウスの尾部において、膵臓特異的遺伝子であるPtf1a遺伝子の異所性過剰発現が生じていることを明らかにした（Semba K et al. 2013）。この結果より我々は胎生期に高血糖の曝露を受けた個体ではPtf1a遺伝子が異所性過剰発現し胎児形態異常を発症する。との仮説を立てた。本研究により糖尿病合併妊娠における胎児形態異常発症機序の一端が明らかになることが期待できる。