Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-06-12 DOI:10.1016/j.tiv.2024.105876

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

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引用次数: 0

Abstract

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.

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方棘霉素通过干扰 MPF 的活性抑制小鼠卵母细胞的减数分裂。

方棘霉素（Fangchinoline，FA）是一种从传统中药防己中提取的生物碱。大量研究表明，方棘霉素对多种癌细胞有毒性作用，但对其对生殖细胞，尤其是卵母细胞的毒性作用却知之甚少。在本研究中，我们研究了方木脂对小鼠卵母细胞成熟的影响及其潜在机制。结果表明，FA 不影响减数分裂的恢复，但抑制了第一个极体的挤出。这种抑制作用不是由于染色体和线粒体等细胞器水平的异常造成的，DNA损伤和活性氧的检测证明了这一点。相反，FA 抑制了无性繁殖促进复合体（APC/C）的活性，这一点从抑制 CCNB1 退化中可以看出。APC/C活性的降低可能是由于CDC25B活性的降低，CDC25B的高磷酸化水平（Ser323）表明了这一点。这可能会进一步提高成熟促进因子（MPF）的活性，而MPF在减数分裂中起着关键作用。总之，我们的研究表明，FA 引起的分裂后期 I 期停滞可能是由于 MPF 和 APC/C 活性异常所致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.