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Analysis of STAT1 expression and biological activity reveals interferon-tau-dependent STAT1-regulated SOCS genes in the bovine endometrium

A. Vitorino Carvalho A , C. Eozenou A , G. D. Healey B , N. Forde C , P. Reinaud A , M. Chebrout A , L. Gall A , N. Rodde D , A. Lesage Padilla A , C. Giraud Delville A , M. Leveugle E , C. Richard A , I. M. Sheldon B , P. Lonergan C , G. Jolivet A and O. Sandra A F

A INRA, UMR1198 Biologie du Développement et Reproduction, F-78350 Jouy-en-Josas, France.
B Centre for Reproductive Immunology, Institute of Life Science, College of Medicine, Swansea University, Swansea, SA2 8PP, UK.
C School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
D INRA, UPR1258 Centre National des Ressources Génomiques Végétales, F-31326 Castanet Tolosan, France.
E INRA, UR1077 Unité Mathématique Informatique et Génome, Jouy-en-Josas, France.
F Corresponding author. Email: olivier.sandra@jouy.inra.fr

Reproduction, Fertility and Development - http://dx.doi.org/10.1071/RD14034
Submitted: 30 January 2014  Accepted: 12 July 2014   Published online: 13 August 2014


 
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Abstract

Signal transducer and activator of transcription (STAT) proteins are critical for the regulation of numerous biological processes. In cattle, microarray analyses identified STAT1 as a differentially expressed gene in the endometrium during the peri-implantation period. To gain new insights about STAT1 during the oestrous cycle and early pregnancy, we investigated STAT1 transcript and protein expression, as well as its biological activity in bovine tissue and cells of endometrial origin. Pregnancy increased STAT1 expression on Day 16, and protein and phosphorylation levels on Day 20. In cyclic and pregnant females, STAT1 was located in endometrial cells but not in the luminal epithelium at Day 20 of pregnancy. The expression of STAT1 during the oestrous cycle was not affected by progesterone supplementation. In vivo and in vitro, interferon-tau (IFNT) stimulated STAT1 mRNA expression, protein tyrosine phosphorylation and nuclear translocation. Using chromatin immunoprecipitation in IFNT-stimulated endometrial cells, we demonstrated an increase of STAT1 binding on interferon regulatory factor 1 (IRF1), cytokine-inducible SH2-containing protein (CISH), suppressor of cytokine signaling 1 and 3 (SOCS1, SOCS3) gene promoters consistent with the induction of their transcripts. Our data provide novel molecular insights into the biological functions of STAT1 in the various cells composing the endometrium during maternal pregnancy recognition and implantation.

Additional keywords: cattle, chromatin immunoprecipitation, implantation, transcription factor, uterus.


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