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Updated: Mar 1, 2026
Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
The toxic effects and possible mechanisms of Brusatol on mouse oocytes
Rujun Ma1, Hongru Li1, Yu Zhang2
1Center for Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Jiangsu, People's Republic of China.
Abstract:
Brusatol is a natural quassinoid that shows a potential therapeutic use in cancer models by the inhibition of Nuclear factor erythroid 2-related factor 2 (Nrf2) and is capable of inducing a variety of biological effects. The effects of Brusatol on oocyte meiosis has not been addressed. In this study, we investigated the impact of Brusatol treatment on mouse oocyte maturation and its possible mechanism. Our data demonstrated that Brusatol treatment disrupted oocyte maturation and spindle/chromosome organization by modulating Nrf2-Cyclin B1 pathway, as the influence of Brusatol was compensated by the addition of Nrf2 activation plasmid, and the mRNA and protein levels of Cyclin B1 were severely reduced in oocytes following Nrf2 decline. In summary, our data support a model that Brusatol, through the inhibition of Nrf2, modulate Cyclin B1 levels, consequently disturbing proper spindle assembly and chromosome condensation in meiotic oocytes.
Insights
Brusatol disrupts mouse oocyte maturation by inhibiting Nuclear factor erythroid 2-related factor 2 (Nrf2), which lowers Cyclin B1 levels. This leads to spindle and chromosome organization defects during meiosis.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Pharmacology
Background:
- Brusatol, a quassinoid, shows anti-cancer potential via Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition.
- The impact of Brusatol on oocyte meiosis remains uninvestigated.
Purpose of the Study:
- To investigate Brusatol's effects on mouse oocyte maturation.
- To elucidate the underlying mechanism involving the Nrf2-Cyclin B1 pathway.
Main Methods:
- Treatment of mouse oocytes with Brusatol.
- Analysis of oocyte maturation, spindle/chromosome organization.
- Investigation of Nrf2 and Cyclin B1 expression levels.
- Utilizing Nrf2 activation plasmid to assess pathway modulation.
Main Results:
- Brusatol treatment disrupted oocyte maturation and spindle/chromosome organization.
- Brusatol's effects were counteracted by Nrf2 activation plasmid.
- Nrf2 inhibition led to significantly reduced Cyclin B1 mRNA and protein levels in oocytes.
Conclusions:
- Brusatol inhibits Nrf2, subsequently modulating Cyclin B1 levels.
- This modulation disrupts spindle assembly and chromosome condensation in meiotic oocytes.
- Brusatol poses a potential risk to female reproductive processes.
