Zhou Changyin, Zhang Xue, ShiYang Xiayan, Wang Huili, Xiong Bo
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.
Aging (Albany NY). 2019 Jul 13;11(13):4706-4719. doi: 10.18632/aging.102084.
DDP (cisplatin), a DNA cross-linking agent, is one of the most common chemotherapeutic drugs that have been widely used in the treatment of sarcomas and germ cell tumors. DDP treatment exhibits severe side effects including renal toxicity, ototoxicity and embryo-toxicity. Women of reproductive age treated with DDP may lead to loss of primordial follicles, resulting in the depletion of the ovarian reserve and consequent premature ovarian failure. However, the influence of DDP on the oocyte quality and the strategy to prevent it has not yet fully clarified. Here, we report that DDP exposure resulted in the oocyte meiotic failure via disrupting the meiotic organelle dynamics and arrangement, exhibiting a prominently impaired cytoskeleton assembly, including spindle formation and actin polymerization. In addition, exposure to DDP led to the abnormal distribution of mitochondrion and cortical granules, two indicators of cytoplasmic maturation of oocytes. Conversely, TP (tea polyphenols) supplementation partially restored all of the meiotic defects resulted from DDP exposure through suppressing the increase of ROS level and the occurrence of DNA damage as well as apoptosis.
顺铂（DDP）是一种DNA交联剂，是最常用的化疗药物之一，已广泛用于治疗肉瘤和生殖细胞肿瘤。顺铂治疗会产生严重的副作用，包括肾毒性、耳毒性和胚胎毒性。接受顺铂治疗的育龄女性可能会导致原始卵泡丢失，从而导致卵巢储备耗尽并继而引发卵巢早衰。然而，顺铂对卵母细胞质量的影响以及预防策略尚未完全阐明。在此，我们报告顺铂暴露通过破坏减数分裂细胞器的动力学和排列导致卵母细胞减数分裂失败，表现为细胞骨架组装明显受损，包括纺锤体形成和肌动蛋白聚合。此外，暴露于顺铂会导致线粒体和皮质颗粒分布异常，这是卵母细胞细胞质成熟的两个指标。相反，补充茶多酚（TP）通过抑制活性氧水平的升高、DNA损伤的发生以及细胞凋亡，部分恢复了顺铂暴露导致的所有减数分裂缺陷。
