2025-03-17 京都大学
<関連情報>
- https://www.kyoto-u.ac.jp/ja/research-news/2025-03-17
- https://www.kyoto-u.ac.jp/sites/default/files/2025-03/web_2503_Watanabe-820cb9b2930cc64deba60797d3596c6f.pdf
- https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00204-9
妊娠中の母体プロゲステロンと脂肪mPRεは胚の栄養状態を制御する Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state
Keita Watanabe∙ Mayu Yamano∙ Junki Miyamoto∙ … ∙ Hiroaki Ohno∙ Eiji Kondoh∙ Ikuo Kimura
Cell Reports Published:March 13, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.115433
Graphical abstract
Highlights
- mPRε is abundant in adipose and mediates progesterone-induced insulin resistance
- mPRε deficiency disrupts glycemic control, causing metabolic disorder in offspring
- Progesterone-activated mPRε in WAT promotes arachidonate release and PGE2 production
Summary
Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPRε) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPRε by increased progesterone during pregnancy enhances maternal insulin resistance via prostaglandin production, efficiently providing glucose to embryos. Correspondingly, the offspring of mPRε-deficient mothers exhibited metabolic dysfunction, whereas mPRε-deficient mothers with high-fat diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo. Additionally, mPRε may represent a modulator for treating pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring.
