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Vitamin C protects carboplatin-exposed oocytes from meiotic failure.
Molecular Human Reproduction ( IF 4 ) Pub Date : 2019-10-28 , DOI: 10.1093/molehr/gaz046
Changyin Zhou 1 , Xue Zhang 1 , Yuwei Zhang 2 , Xiayan ShiYang 1 , Yu Li 1 , Xiaoyan Shi 1 , Bo Xiong 1
Affiliation  

CBP (carboplatin) is a second-generation chemotherapeutic drug of platinum compound commonly applied in the treatment of sarcomas and germ cell tumours. Although it is developed to replace cisplatin, which has been proven to have a variety of side effects during cancer treatment, CBP still exhibits a certain degree of toxicity including neurotoxicity, nephrotoxicity, hematotoxicity and myelosuppression. However, the underlying mechanisms regarding how CBP influences the female reproductive system especially oocyte quality have not yet been fully determined. Here, we report that CBP exposure led to the oocyte meiotic defects by impairing the dynamics of the meiotic apparatus, leading to a remarkably aberrant spindle organisation, actin polymerisation and mitochondrial integrity. Additionally, CBP exposure caused compromised sperm binding and fertilisation potential of oocytes by due to an abnormal distribution of cortical granules and its component ovastacin. More importantly, we demonstrated that vitamin C supplementation prevented meiotic failure induced by CBP exposure and inhibited the increase in ROS levels, DNA damage accumulation and apoptotic incidence. Taken together, our findings demonstrate the toxic effects of CBP exposure on oocyte development and provide a potential effective way to improve the quality of CBP-exposed oocytes in vitro.

中文翻译:

维生素C保护暴露于卡铂的卵母细胞免受减数分裂失败。

CBP(卡铂)是铂化合物的第二代化疗药物,通常用于治疗肉瘤和生殖细胞肿瘤。尽管已开发出替代顺铂的药物,顺铂已被证明在癌症治疗期间具有多种副作用,但CBP仍表现出一定程度的毒性,包括神经毒性,肾毒性,血液毒性和骨髓抑制。然而,关于CBP如何影响女性生殖系统特别是卵母细胞质量的潜在机制尚未完全确定。在这里,我们报道CBP暴露通过损害减数分裂仪的动力学,导致卵母细胞减数分裂缺陷,导致异常异常的纺锤体组织,肌动蛋白聚合和线粒体完整性。另外,CBP暴露由于皮层颗粒及其成分ovastacin的异常分布而导致卵母细胞精子结合和受精能力受损。更重要的是,我们证明了补充维生素C可以防止CBP暴露引起的减数分裂失败,并抑制ROS水平,DNA损伤积累和凋亡发生率的增加。综上所述,我们的发现证明了CBP暴露对卵母细胞发育的毒性作用,并提供了一种潜在的有效方式来提高体外CBP暴露的卵母细胞的质量。DNA损伤累积和凋亡发生率。综上所述,我们的发现证明了CBP暴露对卵母细胞发育的毒性作用,并提供了一种潜在的有效方式来提高体外CBP暴露的卵母细胞的质量。DNA损伤累积和凋亡发生率。综上所述,我们的发现证明了CBP暴露对卵母细胞发育的毒性作用,并提供了一种潜在的有效方式来提高体外CBP暴露的卵母细胞的质量。
更新日期:2019-11-01
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