Pathophysiology of hypertensive disorder of pregnancy through DNA methylation analysis of villous trophoblasts in first trimester

Research Project

Project/Area Number	17K11252
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Obstetrics and gynecology
Research Institution	Showa University
Principal Investigator	Sekizawa Akihiko 昭和大学, 医学部, 教授 (10245839)
Co-Investigator(Kenkyū-buntansha)	川嶋章弘昭和大学, 医学部, 講師 (10783376) 四元淳子昭和大学, 医学部, 特別研究生 (30553648)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	妊娠高血圧症候群 / 絨毛 / 胎盤 / DNAメチル化 / 絨毛細胞 / 妊娠高血圧症侯群 / 妊娠高血圧腎症 / 妊娠初期絨毛 / 絨毛検査
Outline of Final Research Achievements	The villus trophoblasts at 1st trimester of pregnancy have a strong cell proliferation ability especially in the early stages, and then differentiate to function as villi in the placenta. We conducted research based on the hypothesis that DNA methylation plays a major role in this functional differentiation. We collected villus tissues at 6-8 weeks, 10-11 weeks, and late gestation. We also collected the tissues in pregnancy with hypertensive disorder of pregnancy (HDP). Their methylation was profiled by microarray and compared each other. As a result, the involvement of genes related to cell proliferation was presumed, and it was confirmed that deficiency of physiological DNA methylation in the villous trophoblasts at 1st trimester is associated with the pathogenesis of HDP.
Academic Significance and Societal Importance of the Research Achievements	妊娠初期絨毛の生理的な機能変化にDNAメチル化の変化が重要な役割を果たしていることを明らかにした。妊娠初期の生理的なDNAメチル化が起こらないことが、絨毛細胞の機能的な変化につながり、それが妊娠高血圧腎症の病態のもとを形成している可能性が示唆された。DNAメチル化の異常はさまざまな環境因子の影響を受けると推察され、そのメチル化異常の防止がHDPの発症予防につながる可能性があり、今後の研究の進展が期待される。