title: Effect of potential role of p53 on embryo development arrest induced by H2O2in mouse.
abstract: During mammalian embryo development in vitro, mechanism of embryonic development arrest caused by oxidative stress has not been clear so far. The tumor suppressor protein p53 controls cell cycle and programmed cell death by regulating relevant signal pathway. Recent researches revealed that the concentration and distribution of p53 are closely related with reactive oxygen species (ROS). The main objective of this experiment was to explore the role of p53 on embryonic development arrest caused by oxidative stress. Results showed that embryo arrest at two-four-cell stage was significantly increased in the presence of 50 μM H2O2(39.01 ± 2.74 vs. 77.20 ± 5.34%, p < 0.05). Supplementation of N-acetyl-L-cysteine (NAC) obviously reduced the ratio of development arrest (39.01 ± 2.74 vs. 71.18 ± 5.34%, p < 0.05), which was accompanied by an increase in ROS level, and H2O2treatment sharply increased messenger RNA (mRNA) expression and protein levels of p53 and p53-ser15. Further increased transcription of GADD45a and p21, a downstream of p53, has an especially significant effect on the mRNA expression of GADD45a. However, expressions of cdc2 were reduced by H2O2. In addition, using Pifithrin-α (PFT-α), the suppresser of p53, the result showed that GADD45a and p21 were significantly downregulated, but the cell cycle gene cdc2 was significantly upregulated, while the protein level of p53 and p53-ser15 was significantly decreased. Taken together, these results demonstrate that ROS could activate p53 and regulate p53 target genes to influence early embryo development in in vitro culture.
authors.affiliation: Laboratory of Animal Genetic Breeding and Reproduction, Agricultural College of Yanbian University, Yanji, 133002, China.
authors.forename: De-Bao
authors.initials: DB
authors.lastname: Hu
authors.affiliation: Laboratory of Animal Genetic Breeding and Reproduction, Agricultural College of Yanbian University, Yanji, 133002, China.
authors.forename: Zhong-Shu
authors.initials: ZS
authors.lastname: Li
authors.affiliation: Laboratory of Animal Genetic Breeding and Reproduction, Agricultural College of Yanbian University, Yanji, 133002, China.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ali
authors.affiliation: Laboratory of Animal Genetic Breeding and Reproduction, Agricultural College of Yanbian University, Yanji, 133002, China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Xu
authors.affiliation: Laboratory of Animal Genetic Breeding and Reproduction, Agricultural College of Yanbian University, Yanji, 133002, China. nzfang@ybu.edu.cn.
authors.forename: Nan-Zhu
authors.initials: NZ
authors.lastname: Fang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015053:Zygote / Q000187:drug effects
chemical_list: D052160:Benzothiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; D012694:Serine; D006861:Hydrogen Peroxide; C121565:pifithrin; D000111:Acetylcysteine
keywords: De-Bao Hu and Zhong-Shu Li contributed equally to this study.; Early mouse embryo in vitro culture; Mouse; Oxidative stress; P53