Biol Reprod
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BOR - Papers in Press, published online ahead of print June 9, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.029405
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BIOLOGY OF REPRODUCTION 71, 1330–1339 (2004)
DOI: 10.1095/biolreprod.104.029405
© 2004 by the Society for the Study of Reproduction, Inc.

Embryo

Presence of Permanently Activated Signal Transducers and Activators of Transcription in Nuclear Interchromatin Granules of Unstimulated Mouse Oocytes and Preimplantation Embryos1

Sandrine Truchet2,3, Martine Chebrout3, Chakib Djediat3, Juana Wietzerbin4, and Pascale Debey3

USM 503 MNHN,3 UMR 8646 CNRS-MNHN, U565 INSERM, Département Régulation, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75005 Paris, France INSERM U365,4 Institut Curie, 75248 Paris, France

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 (signal transducer and activator of transcription 1) at both the mRNA and protein levels, interferon {gamma} (IFN{gamma}) as well as IFN{alpha} 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{gamma}-target genes, namely interferon regulatory factor-1 (IRF-1) and suppressor of cytokine signaling-1 (SOCS-1) is indeed increased in two-cell embryos in response to IFN{gamma}. 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.

1 Supported by grants from INSERM, Institut Curie, INRA, and MNHN. S.T. was supported by fellowships from the French Ministry of Education and Research (MNRT) and from the Société de Secours des Amis des Sciences.

2 Correspondence: UMR 8646 CNRS-MNHN/U565 INSERM, Muséum National d'Histoire Naturelle, 53 rue Buffon, 75005 Paris, France. FAX: 01 58 41 50 20; Sandrine.Truchet{at}ibpc.fr






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Copyright © 2004 by the Society for the Study of Reproduction.