Characteristic DNA methylation profles of chorionic villi in recurrent miscarriage

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18701
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya City University
• Principal Investigator: MATSUMOTO YOSUKE 名古屋市立大学, 医薬学総合研究院(医学), 助教 (90791294)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 習慣流産 / 絨毛 / 脱落膜 / エピゲノム

Outline of Final Research Achievements

The cause of recurrent miscarriage remains unknown in approximately 25% of cases. We performed a comprehensive DNA methylation analysis of chorionic villi (fetal origin) and decidua (maternal origin) collected at the time of miscarriage from patients with unexplained recurrent miscarriage and found that the DNA methylation profiles of chorionic villi, but not decidua, were different between the recurrent miscarriage group and normal pregnancy group. We identified SPATS2L as a representative gene that differs in DNA methylation between the recurrent miscarriage group and the normal pregnancy group, and found that SPATS2L protein expression was decreased in the trophoblastic cells in the recurrent miscarriage group. Knockdown of SPATS2L also reduced the invasive and migratory ability of trophoblast cells, suggesting that the normal development of embryos is inhibited.

Free Research Field

不育症

Academic Significance and Societal Importance of the Research Achievements

習慣流産の原因となりうる一つの因子として、絨毛のエピゲノム異常が示唆されました。従来原因不明と説明していた患者に、研究的にはエピゲノム異常による流産が存在し、研究対象の習慣流産患者5人全員がその後生児獲得できていることから、その場合は次回妊娠での生児獲得の期待値が高いと説明できます。