Novel mechanisms of pregnancy complications resulting in the innate immune response in the syncytiotrophoblast induced by double-stranded RNA

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K18404
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology; Embryonic/Neonatal medicine
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Motomura Kenichiro 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 共同研究員 (00724329)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 合胞体栄養膜細胞 / 妊娠合併症 / パターン認識受容体 / 二本鎖RNA / 胎盤

Outline of Final Research Achievements

We analyzed the expression and function of double-stranded RNA receptors on human syncytiotrophoblast. The syncytiotrophoblast play a central role in the placental functions. Using primary human term placenta-derived syncytiotrophoblast culture model, we showed that double-stranded RNA (dsRNA) receptors (TLR3, MDA5, RIG-I) are predominantly expressed on the syncytiotrophoblast, and the stimulations via these receptors using a dsRNA analogue, poly:IC induced 1) the production of inflammatory cytokines and chemokines, 2) the production of anti-viral molecules, and 3) caspase 3/7-dependent apoptosis. Moreover, using a pregnant mice model, we demonstrated that intravenous administration of dsRNA induced fetal growth restriction, and this process was turned out to be via TLR 3. These results suggest the link between dsRNA receptors and pregnancy complications and the possibility of double stranded RNA receptors as a novel biomarker or a therapeutic target.

Free Research Field

妊娠と免疫

Academic Significance and Societal Importance of the Research Achievements

炎症が関与する妊娠合併症は未だに原因が明らかになっていないものが多く、これが根治療法の開発を困難にしている。本研究は合胞体栄養膜細胞に発現する二本鎖RNA受容体に着目し、これらを介した刺激が誘導する胎盤での免疫反応の一端を明らかにした。今後臨床検体を用いた検討を組み合わせることで、胎盤障害の新たなメカニズム・バイオマーカーが明らかとなる可能性が示唆された。