2022 Fiscal Year Final Research Report
Molecular mechanisms of the fetal left-right axis malformations induced by maternal hyperglycemia.
| Project/Area Number |
18K07880
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | 糖尿病母体 / 左右軸 / 心臓発生 / 高血糖 |
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| Outline of Final Research Achievements |
The expression of Nodal and Cerl2 was decreased in the node of 8.0-day embryo exposed to high glucose concentration, and it was due to the reduction of active form of NOTCH (NICD) in the node. We focused on Wnt3a which is required for the expression of NOTCH around the node in 8.0-day embryo, and identified two enhancers, PSE1 and PSE2, for primitive streak specific expression of Wnt3a. We first introduced point mutation in Wnt3a PSE1 by CRISPR/Cas9 system, but there was no significant decrease in expression of Wnt3a in the pimitive streak, and the obtained homozygote pups were viable.
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| Free Research Field |
Developmental Biology
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病は先天異常を引き起こすリスク要因であり、形態学的には妊娠７週までに糖尿病による先天異常が生じると考えられている。疫学調査によって糖尿病による胎児の左右形態異常が裏付けれており、実験的には糖尿病モデルマウスの胎児にヒトと同様の左右形態異常が発生することが報告されているが、その発生機序については未だ不明である。我々の研究成果は、妊娠糖尿病が左右軸関連の先天異常発生を引き起こす要因を特定することで、エビデンスに基づいた妊婦への血糖管理や栄養指導に役立てることが可能となる。
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