Entire mitogen activated protein kinase (MAPK) pathway is present in preimplantation mouse embryos

Abstract

To understand how mitogenic signals are transduced into the trophoblasts in preimplantation embryos, the expression of mitogen-activated protein kinase (MAPK) pathway molecules was tested. We used immunocytochemical means and reverse transcriptase-polymerase chain reaction to test whether MAPK pathway molecule gene products exist at the protein and phosphoprotein level in the zygote and the RNA level in the egg and zygote. In addition, all antibodies detected the correct-sized major band in Westerns of placental cell lines representing the most prevalent cell type in preimplantation embryos. A majority of mRNA transcripts of MAPK pathway genes were detected in unfertilized eggs, and all were expressed in the zygote. We found that the MAPK pathway protein set consisting of the following gene products was present: FRS2␣, GRB2, GAB1, SOS1, Ha-ras, Raf1/RafB, MEK1,2,5, MAPK/ERK1,2, MAPK/ERK5, and RSK1,2,3 (see abbreviations). These proteins were detected in trophoblasts in embryonic day (E) 3.5 embryos when they could mediate mitogenic fibroblast growth factor signals from the embryo or colony stimulating factor-1 signals from the uterus.

Mitogen-activated protein kinase (MAPK) blockade of bovine preimplantation embryogenesis requires inhibition of both p38 and extracellular signal-regulated kinase (ERK) pathways

“…It can be concluded that ERK protein was localized in the cytoplasm and the nucleus, suggesting that the ERK pathway is also active in bovine embryos. This finding is different from that in mouse where there are conflicting reports about the role of ERK in preimplantation embryogenesis (Haraguchi et al 1998, Iwamori et al 2000, Wang et al 2004. It has been suggested that ERK is not phosphorylated at any stage during the cell cycle of the mouse early embryos (Iwamori et al 2000); although ERK proteins are expressed, MAPKs other than ERKs are activated during the early cleavage divisions of mouse embryos (Haraguchi et al 1998).…”

“…It has been suggested that ERK is not phosphorylated at any stage during the cell cycle of the mouse early embryos (Iwamori et al 2000); although ERK proteins are expressed, MAPKs other than ERKs are activated during the early cleavage divisions of mouse embryos (Haraguchi et al 1998). However, recently it has been reported that ERK1/2 mRNA could be detected from the oocyte to the blastocyst stage in the mouse embryo and, in addition, ERK1/2 proteins are activated by phosphorylation (Wang et al 2004).…”

Co-localization of neural cell adhesion molecule and fibroblast growth factor receptor 2 in early embryo development

“…5B). It has been shown previously that the entire MAPK pathway is present during mouse preimplantation development (Wang et al, 2004). Interestingly, NCAM stimulation has been shown to phosphorylate and thereby activate ERK1/2 (Kolkova et al, 2000).…”

Preimplantation embryo programming: transcription, epigenetics, and culture environment

“…EGA has long been thought of as a global and promiscuous activation of genes whose regulated repression was then necessary to establish the preimplantation developmental program. Thanks to large-scale transcriptomic analyses, it now appears that a highly regulated gene expression program is initiated as soon as embryonic genome expression begins (Hamatani et al 2004, Wang et al 2004, Zeng et al 2004. Because early perturbations of this 'embryonic program' have long-term significant effects on reproductive performance, we will discuss recent data concerning the regulation of EGA and its importance for long-term development.…”