Details

Autor(en) / Beteiligte

• Gao, Shi-Cai
• Dong, Ming-Zhe
• Zhao, Bing-Wang
• Liu, Sai-Li
• Guo, Jia-Ni
• Sun, Si-Min
• Li, Yuan-Yuan
• Xu, Yuan-Hong
• Wang, Zhen-Bo

Titel

Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity

Ist Teil von

• Toxicology in vitro, 2024-08, Vol.99, p.105876, Article 105876

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity. •FA treatment inhibited the extrusion of first polar body.•FA treatment arrested oocyte at metaphase I stage during maturation.•FA treatment influenced the Securin degradation.•FA did not affect DNA damage and mitochondrial dysfunction in oocytes.•FA affected MPF in oocyte meiosis.