Study on mechanism of placental toxicity of folic acid antagonist, methotrexate

• Project/Area Number: 25450423
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Tottori University
• Principal Investigator: Akihiko Sugiyama 鳥取大学, 農学部, 准教授 (00432609)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 胎盤毒性 / メトトレキサート / 胎盤 / ラット / 葉酸代謝拮抗剤 / 酸化障害 / 細胞死

Outline of Final Research Achievements

We clarified that Methotrexate (MTX) exposure during gestation day (GD) 11-12 induced hypoplasia of placental basal cell layer in rats. In the present study, the histopathological and molecular biological examinations were performed to clarify the pathogenesis of MTX-induced hypoplasia of placental basal cell layer. The suggestions of the present study were as follows: (1) Apoptosis in hypoplasia of placental basal cell layer was induced by ① both extrinsic and intrinsic pathways, ② oxidative damage of protein and unsaturated fatty acid, and ③ activation of JNK(c-Jun N-terminal kinase)pathway, (2) There were no relation between sensibility to MTX of component cells in placenta and expression levels of dihydrofolate reductase.