Embryo

Presence of Permanently Activated Signal Transducers and Activators of Transcription in Nuclear Interchromatin Granules of Unstimulated Mouse Oocytes and Preimplantation Embryos

Abstract
We previously described that mouse oocytes and preimplantation embryos express the two subunits of interferon-gamma receptor. We now report that, despite the presence of STAT1 at both the mRNA and protein levels, IFN as well as IFN are unable to trigger massive nuclear translocation of STAT1 in these cells, even at high cytokine concentrations. Conversely, nuclear accumulation of STAT1 was readily observed in murine L929 somatic cells under the same conditions. However, in the absence of any stimulation, both tyrosine (Y701p) and serine (S727p) phosphorylated forms of STAT1 were already detected in the nuclei of oocytes and early embryos. Phosphorylated STAT1 appeared concentrated in large nuclear dots, which were identified by indirect immunofluorescence and electron microscopy as clusters of interchromatin granules (IGCs or "speckles"). A similar distribution was also observed for the serine (S727p) phosphorylated form of STAT3 as well as for tyrosine (Y689p) phosphorylated STAT2. Western blot analysis confirmed that STAT factors present in mouse oocytes are predominantly phosphorylated. In parallel, we showed that the transcription of two IFN-target genes, namely IRF-1 and SOCS-1 is indeed increased in two-cell embryos in response to IFN. Altogether, our results suggest that, despite the lack of massive nuclear accumulation of STAT1 in response to exogenous IFNs and the permanent presence of phosphorylated STATs in the nucleus, JAK/STAT pathways are functional during early development.

Key words: Embryo • Cytokines • Early development • Signal transducers • Signal transduction