Population Council Research that makes a difference

Abstract

Messenger ribonucleic acid encoding interferon-inducible guanylate binding protein 1 is induced in human endometrium within the putative window of implantation 
Kumar,Sushma; Li,Quanxi; Dua,Anuradha; Ying,Yu-Kang; Bagchi,Milan K.; Bagchi,Indrani C.
Journal of Clinical Endocrinology and Metabolism 86(6): 2420-2427
Publication date: 2001


The putative window of embryo implantation in the human opensbetween days 19-24 of the menstrual cycle. During thisperiod, the endometrium undergoes distinctive structural andfunctional changes orchestrated by steroid hormones, growthfactors, and cytokines to attain a receptive phase in whichit acquires the ability to implant the developing embryo. Amajor challenge in the study of human reproduction is to identifythe molecular signals that participate in the establishmentof this critical receptive phase in the context of the naturalcycle. Toward this goal, we analyzed human endometrial biopsiesat various days of the menstrual cycle by employing messengerRNA (mRNA) differential display technique. We isolated severalcomplementary DNAs representing genes that are either up- ordown-regulated within the putative window of implantation. Weidentified one of these genes as that encoding interferon (IFN)-inducibleguanylate-binding protein 1 (or GBP1), which possesses GTPaseactivity. Analysis of endometrial biopsies by Northern blottingand RT-PCR demonstrated that GBP1 mRNA is specifically inducedat the midsecretory phase of the menstrual cycle. In situ hybridizationanalysis revealed that GBP1 mRNA expression is localized inthe glandular epithelial cells as well as in the stroma in theimmediate vicinity of the glands. We observed that treatmentof human endometrial adenocarcinoma cell, Ishikawa, with IFN-or IFN- markedly induced the expression of GBP1 mRNA. IFN- was,however, a more potent inducer of GBP1 than IFN-. Consistentwith this finding, the temporal profile of GBP1 expression duringthe menstrual cycle resembled that of IFN- mRNA more closelythan that of IFN-, predicting a regulatory role of IFN- in GBP1expression in midsecretory human endometrium. Although the precisefunction of GBP1 in the receptive human uterus remains unclear,its unique expression overlapping the putative window of implantationsuggests that it might serve as a useful marker of uterine receptivityin the human.