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PP2Cδ ( Ppm1d , WIP1), an endogenous inhibitor of p38 MAPK, is regulated along With Trp53 and Cdkn2a following p38 MAPK inhibition during mouse preimplantation development
Author(s) -
Hickson Jenny A.,
Fong Barry,
Watson Patricia H.,
Watson Andrew J.
Publication year - 2007
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20688
Subject(s) - biology , cdkn2a , mapk/erk pathway , embryo , p38 mitogen activated protein kinases , kinase , microbiology and biotechnology , protein kinase a , genetics , gene
Preimplantation embryos utilize mitogen‐activated protein kinase signaling (MAPK) pathways to relay signals from the external environment to prepare appropriate responses and adaptations to a changing milieu. It is therefore important to investigate how MAPK pathways are regulated during preimplantation development. This study was conducted to investigate whether PP2Cδ ( Ppm1d , WIP1) is expressed during mouse preimplantation development and to determine the influences of p38 MAPK inhibition on expression of Trp53 (p53), Ppm1d , (WIP1), and Cdkn2a (p16) during mouse preimplantation development. Our results indicate that Trp53 , Ppm1d , and Cdkn2a mRNAs and TRP53 and PP2Cδ proteins are expressed throughout mouse preimplantation development. Treatment of 2‐cell embryos with SB220025 (potent inhibitor of p38 MAPK α/β/MAPK 14/11) significantly increased Trp53 , Ppm1d and Cdkn2a and Mapk14 mRNA levels at 12 and 24 hr. Treatment of 8‐cell embryos with SB220025 for 12 hr increased Trp53 , Ppm1d , and Cdkn2a mRNA levels, but not Mapk14 mRNA levels. Treatment of 8‐cell embryos for 24 hr increased Trp53 , and Ppm1d mRNA levels, but decreased Cdkn2a and Mapk14 mRNA levels. Therefore, blockade of p38 MAPK activity is associated with embryo stage specific influences on Trp53 , Ppm1d , Cdkn2a , and Mapk14 expression during mouse preimplantation development. These results define downstream targets of p38 MAPK during preimplantation development and indicate that the p38 MAPK pathway regulates Trp53 , Ppm1d , and Cdkn2a expression. This study increases our understanding of the mechanisms controlling preimplantation development and of the interactions between preimplantation embryos and their culture environments. Mol. Reprod. Dev. 74: 821–834, 2007. © 2007 Wiley‐Liss, Inc.