A role of Sonic hedgehog pathway in preeclamptic placenta

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: Tatsumi Keiji 京都大学, 医学研究科, 非常勤講師 (10324633)
• Co-Investigator(Kenkyū-buntansha): 近藤 英治 京都大学, 医学研究科, 准教授 (10544950) ; 小西 郁生 京都大学, 医学研究科, 名誉教授 (90192062)
• Research Collaborator: Mogami Haruta
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: foetal growth / sonic hedgehog / placenta / preeclampsia

Outline of Final Research Achievements

The expression of both PTCH1 and GLI2, active markers for SHH pathway activity, was significantly lower in preeclampsia placentas compared with normal placentas and PTHC1 was highly correlated with birth weight and placental weight. These data suggest that the SHH pathway is suppressed in preeclampsia placentas and that it affects birth weight. Recombinant SHH promoted syncytialization in primary cytotrophoblast and SHH pathway inhibitor, cyclopamine suppressed syncytialization. The direct injection of cyclopamine into mice placentas decreased PTCH1 and decreased birth weight in mice. Since the placental SHH pathway regulated foetal growth, this finding could provide a clue to the development of new treatments for major placenta-related disorders, including preeclampsia and FGR.

Free Research Field

周産期

Academic Significance and Societal Importance of the Research Achievements

胎児発育の成否は、主に胎盤機能に依存している。胎盤機能が著しく低下すると、胎児発育不全や妊娠高血圧腎症を引き起こし、早期の娩出を余儀なくされるため、脳や肺など主要臓器の機能が未熟であり、児の死亡率、合併症罹患率が高くなる。しかし、これまで胎盤機能低下に関与する分子生物学的機序は未解明な部分が多く、有効な治療法の開発にも至っていない。本研究では、胎盤機能においてSHH pathwayが胎児発育に寄与している可能性が示され、胎児発育不全や妊娠高血圧腎症に対する予防、新規治療法の開発につながる可能性が示された。