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

The putative window of embryo implantation in the human opens between days 19-24 of the menstrual cycle. During this period, the endometrium undergoes distinctive structural and functional changes orchestrated by steroid horm ones, growth factors, and cytokines to attain a receptive phase in which if acquires the ability to implant the developing embryo. A major challenge i n the study of human reproduction is to identify the molecular signals that participate in the establishment of this critical receptive phase in the c ontext of the natural cycle. Toward this goal, we analyzed human endometria l biopsies at various days of the menstrual cycle by employing messenger RN A (mRNA) differential display technique. We isolated several complementary DNAs representing genes that are either up- or down-regulated within the pu tative window of implantation. We identified one of these genes as that enc oding interferon (IFN)-inducible guanylate-binding protein 1 (or GBP1), whi ch 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 analys is revealed that GBP1 mRNA expression is localized in the glandular epithel ial cells as well as in the stroma in the immediate vicinity of the glands. We observed that treatment of human endometrial adenocarcinoma cell, Ishik ama, with IFN-gamma or IFN-alpha markedly induced the expression of GBP1 mR NA. IFN-gamma was, however, a more potent inducer of GBP1 than IFN-alpha. C onsistent with this finding, the temporal profile of GBP1 expression during the menstrual cycle resembled that of IFN-gamma mRNA more closely than tha t of IFN-alpha, predicting a regulatory role of IFN-gamma in GBP1 expressio n in midsecretory human endometrium. Although the precise function of GBP1 in the receptive human uterus remains unclear, its unique expression overla pping the putative window of implantation suggests that it might serve as a useful marker of uterine receptivity in the human.