Study on the mechanism of feto-maternal communication via micro-RNA

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Miyasaka Naoyuki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70313252)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Nik-related kinase / 分娩遅延 / ノックアウトマウス / 絨毛合胞体細胞層

Outline of Final Research Achievements

We investigated the mechanism responsible for the delayed delivery in Nik-related kinase (Nrk)-knockout mice. By comparing the expressed genes in the term placenta between Nrk-knockout and control mice, we found that progestin and adipo Q receptor family member 9, and prolactin family members were upregulated and prostaglandin synthase cyclooxygenase 2 was down regulated in Nrk-knock out mice. Electron microscopic study showed that placental Golgi bodies in Nrk-knockout were significantly enlarged, which indicated secretion dysfunction of the placental products might be the cause of delayed delivery. Moreover, we found that insufficient progesterone reduction at term was the main reason for the delayed delivery in Nrk-knockout mice. In addition, we investigated Nrk expression in the human placenta in order to evaluate whether Nrk was associated with the post term pregnancy. It was revealed the Nrk was also expressed in syncytial trophoblasts in human placenta.

Free Research Field

周産期医学

Academic Significance and Societal Importance of the Research Achievements

妊娠42週以降の過期妊娠は母児の周産期予後が極めて不良であるが、ヒトにおける陣痛発来のメカニズムは未だに解明されていない。Nrk-knockout胎仔を正常母体に移植したマウスにおいて高率に分娩遅延が発生し母児の死亡率が高いことから、胎仔もしくは胎盤から何らかのシグナルが母体に作用して陣痛が開始されていることが示唆される。本研究ではNrkが陣痛発来を抑制するプロゲステロン関連の遺伝子を増強し、陣痛発来を促進するプロスタグランジン関連遺伝子を抑制することで分娩遅延を来すことを初めて証明した。また、Nrkがヒト胎盤においても母体血と接触する合胞体絨毛細胞に発現していることを世界に先駆けて証明した。