Role of the lysophospholipid pathway in trophoblast function and pathologic mechanism of preeclampsia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18227
• 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: Nara Medical University
• Principal Investigator: Ichikawa Mayuko 奈良県立医科大学, 医学部, 助教 (30833678)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: リゾリン脂質 / 胎盤機能不全 / 妊娠高血圧症候群 / オートタキシン / LPA3

Outline of Final Research Achievements

In the placentas of normal pregnancy and hypertensive disorder of pregnancy (HDP), oxidative stress increased with gestational week and antioxidant capacity decreased. In relation to serum ATX concentration, both normal pregnancy and HDP showed a positive correlation with oxidative stress, while antioxidant capacity showed a negative correlation in the HDP group. By gestational age, the correlation between serum ATX concentration and oxidative stress markers was more pronounced in the third trimester of pregnancy. Oxidative stress stimulation of the trophoblast cell line induced ATX mRNA expression, and LPA signaling stimulation reduced accumulation of reactive oxygen species in the cells.
The placental ATX-LPA pathway was suggested to play a role in regulating placental function to appropriate levels for fetal development by regulating oxidative stress, thereby affecting immune regulation and cell differentiation.

Free Research Field

妊娠高血圧症候群

Academic Significance and Societal Importance of the Research Achievements

胎盤のATX-LPA経路は酸化ストレスを調整することにより免疫調整や細胞分化に影響を与え、胎盤機能を胎児発育のために適切なレベルに調整する役割を担っていることが示唆された。
これまで、胎盤機能を適切に評価できるマーカーは報告されていなかった。妊娠中の血清ATX濃度の測定は、胎盤機能を評価するための有用なバイオマーカーの候補となり得る。今後は、妊娠高血圧症候群のみならず、胎盤機能と関連する子宮内胎児発育遅延等の症例においても、血清ATX濃度の測定が有用である可能性がある。