Messenger ribonucleic acid encoding interferon-inducible guanylate binding protein 1 is induced in human endometrium within the putative window of implantation

The putative window of embryo implantation in the human opens between clays 19-24 of the menstrual cycle. During this period, the endometrium undergoes distinctive structural and functional changes orchestrated by steroid hormones, growth factors, and cytokines to attain a receptive phase in which it acquires the ability to implant the developing embryo. A major challenge in the study of human reproduction is to identify the molecular signals that participate in the establishment of this critical receptive phase in the context of the natural cycle. Toward this goal, we analyzed human endometrial biopsies at various days of the menstrual cycle by employing messenger RNA (mRNA) differential display technique. We isolated several complementary DNAs representing genes that are either up- or down-regulated within the putative window of implantation. We identified one of these genes as that encoding interferon (IFN)-inducible guanylate-binding protein 1 (or GBP1), which possesses GTPase activity. Analysis of endometrial biopsies by Northern blotting and RT-PCR demonstrated that GBP1 mRNA is specifically induced at the midsecretory phase of the menstrual cycle. In situ hybridization analysis revealed that GBP1 mRNA expression is localized in the glandular epithelial cells as well as in the stroma in the immediate vicinity of the glands. We observed that treatment of human endometrial adenocarcinoma cell, Ishikawa, with IFN-γor IFN-α markedly induced the expression of GBP1 mRNA. IFN-γ was, however, a more potent inducer of GBP1 than IFN-α. Consistent with this finding, the temporal profile of GBP1 expression during the menstrual cycle resembled that of IFN-γ mRNA more closely than that of IFN-α, predicting a regulatory role of IFN-γ in GBP1 expression in midsecretory human endometrium. Although the precise function of GBP1 in the receptive human uterus remains unclear, its unique expression overlapping the putative window of implantation suggests that it might serve as a useful marker of uterine receptivity in the human.