Development of a new treatment model for placental dysfunction

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: ISOTANI Ayako 奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (20444523)
• Research Collaborator: IKAWA masahito ; YURI syunsuke
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胎盤 / 不妊治療 / 動物モデル

Outline of Final Research Achievements

The placenta is an essential organ for supporting the growth of a fetus in the mother's body. Placental dysfunction causes repeated abortions and infertility. However, a method for the treatment of these conditions has not yet been established. In this study, Ets2 mutant mice were produced using genome editing technology, as a placental dysfunction model. A drug-inducible Cdx2-expressing embryonic stem (ES) cell line was established for use in the development of a new placental dysfunction treatment model. The ES cells were injected into an eight-cell embryo and made to express Cdx2 with the same timing as that of embryonic development. Although most of the ES-derived cells could not differentiate into trophoblasts, which are stem cells of the placenta, we observed that some of the Cdx2-expressed ES cells could differentiate into trophoblasts.
With further improvement, these results may provide a basis for establishing and developing a new placental dysfunction treatment model.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

胎盤機能不全モデルとして新に樹立したEts2変異マウスは、先行研究の表現型と異なる表現型を示した。遺伝型を比較解析することで表現型につながるEts2の分子生物学的な役割が明らかになっていくものと考えられる。薬剤誘導型Cdx2-ES細胞は、初期胚期の短時間でCdx2だけでは胎盤の元となる栄養芽細胞への分化は不十分であったが、一部、栄養芽細胞へ分化するものも認められた。さらなる工夫により、ES細胞が胎盤機能不全レスキューモデルに適用できる可能性が示唆された。