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Updated: Feb 16, 2026
Loss- and Gain-of-function Approach to Investigate Early Cell Fate Determinants in Preimplantation Mouse Embryos
Published on: June 6, 2016
Nrf2 inhibition affects cell cycle progression during early mouse embryo development
Ying Lin1,2, Liu-Cai Sui1, Rong-Hua Wu1
1Reproductive Medical Center, Jinling Hospital, Clinical School of Medical College, Nanjing University, Jiangsu 210002, People's Republic of China.
Abstract:
Brusatol, a quassinoid isolated from the fruit of Bruceajavanica, has recently been shown to inhibit nuclear factor erythroid 2-related factor 2 (Nrf2) via Keap1-dependent ubiquitination and proteasomal degradation or protein synthesis. Nrf2 is a transcription factor that regulates the cellular defense response. Most studies have focused on the effects of Nrf2 in tumor development. Here, the critical roles of Nrf2 in mouse early embryonic development were investigated. We found that brusatol treatment at the zygotic stage prevented the early embryo development. Most embryos stayed at the two-cell stage after 5 days of culture (P < 0.05). This effect was associated with the cell cycle arrest, as the mRNA level of CDK1 and cyclin B decreased at the two-cell stage after brusatol treatment. The embryo development potency was partially rescued by the injection of Nrf2 CRISPR activation plasmid. Thus, brusatol inhibited early embryo development by affecting Nrf2-related cell cycle transition from G2 to M phase that is dependent on cyclin B-CDK1 complex.
Insights
Brusatol halts early mouse embryo development by inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2). This Nrf2 inhibition causes cell cycle arrest, preventing crucial cell division for embryonic growth.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Developmental Biology
Background:
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor crucial for cellular defense mechanisms.
- While Nrf2's role in tumor development is extensively studied, its function in early embryogenesis remains less understood.
- Brusatol, a quassinoid from Brucea javanica, is known to inhibit Nrf2 activity.
Purpose of the Study:
- To investigate the critical roles of Nrf2 in mouse early embryonic development.
- To determine the effects of brusatol, an Nrf2 inhibitor, on zygotic development.
- To elucidate the molecular mechanisms underlying brusatol-induced developmental arrest.
Main Methods:
- Treatment of mouse zygotes with brusatol.
- Assessment of early embryo development and cell cycle progression.
- Quantitative analysis of cell cycle-related gene expression (CDK1, cyclin B).
- Rescue experiments using Nrf2 CRISPR activation plasmid injection.
Main Results:
- Brusatol treatment significantly inhibited early mouse embryo development, with most embryos arresting at the two-cell stage.
- This developmental arrest was correlated with cell cycle arrest.
- mRNA levels of CDK1 and cyclin B were reduced in brusatol-treated embryos.
- Partial rescue of embryo development was observed upon Nrf2 activation via CRISPR plasmid injection.
Conclusions:
- Brusatol inhibits early mouse embryonic development by targeting Nrf2.
- The mechanism involves Nrf2-dependent cell cycle arrest at the G2 to M phase transition, mediated by the cyclin B-CDK1 complex.
- Nrf2 plays a critical role in regulating cell cycle progression essential for early embryonic development.
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