title: Inhibition of phosphorylated Ser473-Akt from translocating into the nucleus contributes to 2-cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis.
abstract: Phosphorylated Ser473-Akt (p-Ser473-Akt) is extensively studied as a correlate for the activity of Akt, which plays an important role in mouse oogenesis and preimplantation embryogenesis. However, little progress has been made about its effect on the mouse zygotic genome activation (ZGA) of 2-cell stage in mouse preimplantation embryos. In this study, we confirmed its localization in the pronuclei of 1-cell embryos and found that p-Ser473-Akt acquired prominent nucleus localization in 2-cell embryos physiologically. Akt specific inhibitors API-2 and MK2206 could inhibit the development of mouse preimplantation embryos in vitro, and induce 2-cell arrest at certain concentrations. 2-cell embryos exposed to 2.0 μmol/L API-2 or 30 μmol/L MK2206 displayed attenuated immunofluorescence intensity of p-Ser473-Akt in the nucleus. Simultaneously, qRT-PCR results revealed that 2.0 μmol/L API-2 treatment significantly downregulated the mRNA pattern of MuERV-L and eIF-1A, two marker genes of ZGA, suggesting a defect in ZGA compared with that of control group. Collectively, our work demonstrated the nuclear localization of p-Ser473-Akt during major ZGA, and Akt specific inhibitors API-2 and MK2206 which led to 2-cell arrest inhibited p-Ser473-Akt from translocating into the nucleus of 2-cell embryos with defective ZGA as well, implying p-Ser473-Akt may be a potential player in the major ZGA of 2-cell mouse embryos.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Junming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Lian
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Jianen
authors.initials: J
authors.lastname: Wei
authors.affiliation: Cellular and Developmental Engineering Center, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Pang
authors.affiliation: Cellular and Developmental Engineering Center, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Chanchan
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.|Cellular and Developmental Engineering Center, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Shie
authors.initials: S
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002747:Chlorpropamide / Q000031:analogs & derivatives / Q000494:pharmacology; D046149:Embryo Culture Techniques; D047108:Embryonic Development; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D016678:Genome / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000378:metabolism; D015053:Zygote / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000096926:Benzenesulfonamides
chemical_list: D002747:Chlorpropamide; D015977:Eukaryotic Initiation Factor-1; D006575:Heterocyclic Compounds, 3-Ring; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; C111224:API 2; D000096926:Benzenesulfonamides; C548887:MK 2206; C499132:MuERV-L protein, mouse; C026022:eukaryotic peptide initiation factor-1A
keywords: 2-cell arrest; mouse; phosphorylated Ser473-Akt; preimplantation embryogenesis; zygotic genome activation