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Abstract

Identification and implantation stage-specific expression of an interferon-a-regulated gene in human and rat endometrium (PDF) (HTML) 
Li,Quanxi; Zhang,Meilin; Kumar,Sushma; Zhu,Li-Ji; Chen,Dahu; Bagchi,Milan K.; Bagchi,Indrani C.
Endocrinology 142(6): 2390-2400
Publication date: 2001

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Implantation of the developing blastocyst is regulated by multiple effectors,such as steroid hormones, growth factors, and cytokines. To understandhow these diverse signaling pathways interact to modulate uterinegene expression, we employed a gene expression screen technique toidentify the molecules that are induced in the periimplantationrat uterus. Here we report the isolation of a complementaryDNA representing a novel gene, interferon-regulated gene 1 (IRG1).This gene exhibits significant homology to interferon (IFN)-/ß-induciblehuman genes p27 and 6-16, indicating that these genesmay belong to the same family. Consistent with this finding,expression of IRG1 messenger RNA (mRNA) in rat uterus increasedabout 20-fold in response to IFN. Uterine expression of IRG1was also stimulated by estrogen and was partially inhibitedby an antiestrogen, ICI 182,780. In pregnant rats, IRG1 expressionwas high on day 1, but declined on days 2 and 3. The level ofIRG1 mRNA again rose transiently on day 4 immediately precedingimplantation. In situ hybridization analysis localized the IRG1mRNA expression in the endometrial epithelium and the surroundingstroma. Interestingly, the expression of p27, which shows highhomology to IRG1, was strongly enhanced in human endometriumduring the midsecretory phase of the menstrual cycle, overlappingthe putative window of implantation. Both IRG1 and p27 mRNAsare therefore induced in the endometrium in an implantationstage-specific manner. We also observed a synergistic interactionbetween IFN and estrogen receptor signaling pathways that ledto maximal induction of p27 mRNA in Ishikawa cells. Althoughthe functional roles of IRG1 and p27 remain unclear, we describefor the first time, identification of a gene family regulatedby IFN in both rodent and human uteri. More importantly, ourstudies reveal that a complex interplay between the steroidhormone and IFN pathways regulates the expression of these genesin the endometrium at the time of implantation.

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