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Identification of Genes in the Ovine Endometrium Regulated by Interferon Independent of Signal Transducer and Activator of Transcription 1

Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, Texas 77843

Address all correspondence and requests for reprints to: Thomas E. Spencer, Center for Animal Biotechnology and Genomics, 442 Kleberg Center, 2471 TAMU, Texas A&M University, College Station, Texas 77843-2471. E-mail: tspencer{at}tamu.edu.

Interferon (IFN), a type I IFN produced by the conceptus trophectoderm, increases many type I IFN-stimulated genes (ISGs) in the ovine uterine endometrial stroma and glandular epithelium (GE) using signal transducer and activator of transcription 1 (STAT1)-dependent pathways. Most ISGs are not induced or increased by IFN in the STAT1-negative endometrial luminal epithelium (LE). The objective was to identify genes regulated by IFN in a STAT1-independent manner using DNA microarray and human cell lines. The RNA from human 2fTGH and U3A (STAT1 null 2fTGH) cell lines, stimulated for 24 h with nothing or recombinant ovine IFN, was profiled using an Affymetrix human genome U95Av2 microarray. In 2fTGH cells, IFN increased the expression of 101 genes at least 2-fold, including IFN-inducible 56-kDa protein (IFI56), ISG12 or p27, and guanylate binding protein isoform I (GBP-2). In U3A cells, IFN increased expression of 66 genes at least 2-fold, including Wnt7a. Steady-state levels of IFI56, ISG12, GBP-2, and Wnt7a mRNAs increased in the ovine uterine endometrium between d 10 and 16 of pregnancy but not during the estrous cycle. GBP-2 and IFI56 mRNAs were expressed only in endometrial stroma, ISG12 in both LE and GE, and Wnt7a only in LE of the ovine uterus. Intrauterine infusion of ovine IFN increased expression of all four genes in the endometrium of cyclic ewes. Therefore, IFN does regulate genes independent of STAT1 in the endometrial LE and U3A cells and dependent on STAT1 in the endometrial stroma and 2fTGH cells. These IFN -stimulated genes may be important in establishment of uterine receptivity to the embryo and conceptus implantation given their stage-specificity in endometrium across diverse species.

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