title: Abnormality of maternal-to-embryonic transition contributes to MEHP-induced mouse 2-cell block.
abstract: Mono (2-ethylhexyl) phthalate (MEHP), an environmental contaminant, is known to cause many serious diseases, especially in reproductive system. However, little is known about the effect of MEHP on preimplantation embryo development. In this study, we found that the development of mouse 2-cell embryo was blocked by 10(-3)  M MEHP. A significant increase in the level of reactive oxygen species (ROS) was observed in arrested 2-cell embryo following 10(-3)  M MEHP treatment for 24 h. However, antioxidants, catalase (CAT), and superoxide dismutase (SOD), reduced intracellular ROS and protected MEHP-exposed embryos from death but failed to return the arrested embryos. Further experiments demonstrated that the level of apoptosis was not altered in live arrested 2-cell embryo and increased in dead arrested 2-cell embryo after MEHP treatment, which implied that ROS and apoptosis were not related with 2-cell block. During analysis of the indicators of embryonic genome activation (EGA) initiation (Hsc70, MuERV-L, Hsp70.1, eIF-1A, and Zscan4) and maternal-effect genes (OCT4 and SOX2), we found that MEHP treatment could significantly decline Hsc70, MuERV-L mRNA level and SOX2 protein level, and markedly enhance Hsp70.1, eIF-1A, Zscan4 mRNA level, and OCT4 protein level at 2-cell to 4-cell stage. Supplementation of CAT and SOD did not reverse the expression tendency of EGA related genes. Collectively, this study demonstrates for the first time that MEHP-induced 2-cell block is mediated by the failure of EGA onset and maternal-effect genes, not oxidative stress and apoptosis.
authors.affiliation: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Chu
authors.forename: Shi
authors.initials: S
authors.lastname: Tian
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Hao
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Xia
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015977:Eukaryotic Initiation Factor-1; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; C499132:MuERV-L protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C026022:eukaryotic peptide initiation factor-1A; C081884:heat-shock protein 70.1; D004051:Diethylhexyl Phthalate; D002374:Catalase; D013482:Superoxide Dismutase; C016599:mono-(2-ethylhexyl)phthalate