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Inhibition of phosphorylated Ser473‐Akt from translocating into the nucleus contributes to 2‐cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis
Author(s) -
Chen Junming,
Lian Xiuli,
Du Juan,
Xu Songhua,
Wei Jianen,
Pang Lili,
Song Chanchan,
He Lin,
Wang Shie
Publication year - 2016
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12273
Subject(s) - protein kinase b , maternal to zygotic transition , microbiology and biotechnology , embryo , biology , akt1 , phosphorylation , embryogenesis , zygote
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 MK 2206 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 MK 2206 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 Mu ERV ‐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 MK 2206 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.