Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles  

作　　者：Xiao Zhang Xue Qing Wu Shuang Lu Ying Lu Guo Xu Ma 

机构地区：[1]Peking University First Hospital,Institute of Urology of Peking University,Beijing 100034,China [2]Reproductive and Genetic Center of Peking University First Hospital,Beijing 100034,China [3]Department of Obstetrics and Gynecology,Shanxi Medical University Second Hospital,Taiyuan 030000,China [4]Reproductive and Genetic Center of National Research Institute for Family Planning,Beijing 100038,China [5]Department of Genetics,Peking Union Medical College,Beijing 100038.China [6]WHO Collaborative Center for Research in Human Reproduction,Beijing 100038,China

出　　处：《Cell Research》2006年第10期841-850,共10页细胞研究(英文版)

摘　　要：Although the role of oxidative stress in maternal aging and infertility has been suggested, the underlying mechanisms are not fully understood. The present study is designed to determine the relationship between mitochondrial function and spindle stability in metaphase II (MII) oocytes under oxidative stress. MII mouse oocytes were treated with H2O2 in the presence or absence of permeability transition pores (PTPs) blockers cyclosporin A (CsA). In addition, antioxidant N-acetylcysteine (NAC), F0/F1 synthase inhibitor oligomycin A, the mitochondria uncoupler carbonyl cyanide 4-trifluoro- methoxyphenylhydrazone (FCCP) or thapsigargin plus 2.5 mM Ca^2+ (Th+2.5 mM Ca^2+) were used in mechanistic studies. Morphologic analyses of oocyte spindles and chromosomes were performed and mitochondrial membrane potential (AWm), cytoplasmic free calcium concentration ([Ca^2+]c) and cytoplasmic ATP content within oocytes were also assayed. In a time- and H202 dose-dependent manner, disruption of meiotic spindles was found after oocytes were treated with H202, which was prevented by pre-treatment with NAC. Administration of H2O2 led to a dissipation of AWm, an increase in [Ca^2+]c and a decrease in cytoplasmic ATP levels. These detrimental responses of oocytes to H2O2 treatment could be blocked by pre-incubation with CsA. Similar to H2O2, both oligomycin A and FCCP dissipated AWm, decreased cytoplasmic ATP contents and disassembled MII oocyte spindles, while high [Ca^2+]c alone had no effects on spindle morphology. In conclusion, the decrease in mitochondria-derived ATP during oxidative stress may cause a disassembly of mouse MII oocyte spindles, presumably due to the opening of the mitochondrial PTPs.

关 键 词：spindle oxidative stress mitochondria permeability transition pore ATP 

分 类 号：Q25[生物学—细胞生物学]