title: Pifithrin-α ameliorates resveratrol-induced two-cell block in mouse preimplantation embryos in vitro.
abstract: Treatment with resveratrol at concentrations greater than 0.5 μmol/L resulted in the arrest of mouse embryo development at the two-cell stage. Resveratrol-induced cytotoxicity was investigated in embryos by evaluating morphologic features by using the bromodeoxyuridine assay and acridine orange and ethidium bromide double staining. Resveratrol was found to significantly increase the expressions of p53, p21, Atf3, smac/Diablo, Bax, Bak1, Bok, and Noxa mRNA in the embryos, whereas Cullin 3 and Cdk1 expressions were decreased. Furthermore, active p53 positive signal in embryos arrested at the two-cell stage was localized in the nucleus, whereas no active p53 signal was observed in control embryos. Pretreatment with pifithrin-α, a p53 inhibitor, downregulated active p53 in two-cell embryo nuclei and ameliorated approximately 50% of the embryonic developmental defect caused by resveratrol. The findings of the present study, therefore, suggest that pifithrin-α could be used as an effective cytoprotective agent against a reproductive toxin such as resveratrol.
authors.affiliation: Department of Animal Biotechnology, KonKuk University, Seoul, Republic of Korea.
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.affiliation: Department of Animal Biotechnology, KonKuk University, Seoul, Republic of Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Kang
authors.affiliation: Department of Animal Biotechnology, KonKuk University, Seoul, Republic of Korea.
authors.forename: Sangiliyandi
authors.initials: S
authors.lastname: Gurunathan
authors.affiliation: Department of Animal Biotechnology, KonKuk University, Seoul, Republic of Korea.
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Animal Biotechnology, KonKuk University, Seoul, Republic of Korea.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, RDA, Gyeonggi-do, Republic of Korea.
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, KonKuk University, Seoul, Republic of Korea. Electronic address: jhkim541@konkuk.ac.kr.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D001755:Blastocyst / Q000187:drug effects*; D019610:Cytoprotection; D004622:Embryo, Mammalian / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
chemical_list: D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin; D000077185:Resveratrol
keywords: Apoptosis; Pifithrin-α; Preimplantation embryo; Resveratrol; Two-cell block; p53