Elucidating the anti-viral responses and host defense mechanisms in the placenta using primary human villous trophoblasts

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20982
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• 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, 研究員 (00724329)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 栄養膜細胞 / 胎盤 / ウイルス感染症 / 自然免疫 / 初代培養 / 妊娠合併症

Outline of Final Research Achievements

Viral infections during pregnancy result in congenital infections and complications, causing lasting adverse effects on both the mother and child. The mechanisms behind this are poorly understood. To address this, we investigated the antiviral responses of syncytiotrophoblast (STB) to understand how viruses infect the fetus and damage the placenta. Using primary human cytotrophoblasts (CTBs), our transcriptome analysis revealed that the STB initiates an antiviral response when stimulated by synthetic double-stranded RNA (dsRNA). This dsRNA also induced cell death in the STB. Furthermore, the impact of viral infections and cellular damage from adeno-associated viruses varied among different serotypes. Our in vivo studies demonstrated that administering dsRNA to pregnant mice caused placental damage and pregnancy complications. These findings shed light on the antiviral defense mechanisms in the placenta and provide a causal link between viral infection and pregnancy complications.

Free Research Field

周産期免疫学

Academic Significance and Societal Importance of the Research Achievements

妊娠中のウイルス感染症は、先天性感染症や妊娠合併症を引き起こすことが知られており、長期的に母児の健康に悪影響を与える。胎盤は胎児をこれらの先天性感染症から保護しているが、そのメカニズムは明らかになっていない。本研究により、胎盤の抗ウイルス機構と、ウイルスによる妊娠合併症発症機序の一端が明らかとなった。これにより、将来的に妊娠中のウイルス感染に伴う先天性感染症や妊娠合併症の予防方法や、治療戦略の策定に資する可能性がある。