title: Mediating effect of ROS on mtDNA damage and low ATP content induced by arsenic trioxide in mouse oocytes.
abstract: Mitochondria provide most of the adenosine triphosphates (ATP) necessary for the maturation of oocytes. Various environmental toxicants would lead damage to mitochondrial DNA (mtDNA) and hence interfere with oocytes development. In the current study, the effect of arsenic trioxide (As2O3) on the common 3867 bp deletion and the copy number of mtDNA in mitochondria of mouse oocytes in vivo or in vitro, as well as the molecular pathway leading to the damage were investigated. PCR strategy was used to detect the damage of mtDNA. Reactive oxygen species (ROS) and ATP content in oocytes were checked to determine the influence of As2O3 on oxidative stress and activity of mitochondria. The results showed that As2O3 could obviously decrease the copy number of mtDNA and cause severe 3867 bp deletion in mitochondria together with elevated ROS level, while ATP content was decreased. Co-treatment with N-Acetyl-Cysteine (NAC) efficiently eliminated ROS induced by As2O3, lessened the mtDNA damage and enhanced ATP content in mouse oocytes both in vivo and in vitro. Taken together, the present study revealed that As2O3 could cause severe mtDNA damage and decrease ATP content by inducing excessive ROS, and this damage would then probably restrain the further development of mouse oocytes.
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Zhang
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: An
authors.forename: Dejun
authors.initials: D
authors.lastname: Huang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qi
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals; D004249:DNA Damage / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D001152:Arsenicals; D004272:DNA, Mitochondrial; D010087:Oxides; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D000077237:Arsenic Trioxide; D000111:Acetylcysteine