At implantation the endometrium undergoes modifications necessary for its physical interactions with the trophoblast as well as the development of the conceptus. We aim to identify endometrial factors and pathways essential for a successful implantation in the caruncular (C) and the intercaruncular (IC) areas in cattle. Using a 13,257-element bovine oligonucleotide array, we established expression profiles at day 20 of the estrous cycle or pregnancy (implantation), revealing 446 and 1,295 differentially expressed genes (DEG) in C and IC areas, respectively (false discovery rate ϭ 0.08). The impact of the conceptus was higher on the immune response function in C but more prominent on the regulation of metabolism function in IC. The C vs. IC direct comparison revealed 1,177 and 453 DEG in cyclic and pregnant animals respectively (false discovery rate ϭ 0.05), with a major impact of the conceptus on metabolism and cell adhesion. We selected 15 genes including C11ORF34, CXCL12, CXCR4, PLAC8, SCARA5, and NPY and confirmed their differential expression by quantitative RT-PCR. The cellular localization was analyzed by in situ hybridization and, upon pregnancy, showed gene-specific patterns of cell distribution, including a high level of expression in the luminal epithelium for C11ORF34 and MX1. Using primary cultures of bovine endometrial cells, we identified PTN, PLAC8, and CXCL12 as interferon-(IFNT) target genes and MSX1 and CXCR7 as IFNT-regulated genes, whereas C11ORF34 was not an IFNT-regulated gene. Our transcriptomic data provide novel molecular insights accounting for the biological functions related to the C or IC endometrial areas and may contribute to the identification of potential biomarkers for normal and perturbed early pregnancy.transcriptome; interferon-tau; pregnancy; cattle IN MAMMALS, the establishment and maintenance of pregnancy require a subtle and tightly regulated communication between the conceptus (embryo and embryonic annexes) and the maternal environment (85). The success of implantation relies on several essential steps including the adjustment of the uterine environment to support the development of the conceptus and the profound remodeling of the endometrium structure necessary for the apposition, adhesion, and invasion phases (36). In contrast to human and rodents, the invasion of the maternal tissue by the fetal tissue is very limited in ruminants (71) and leads to a synepitheliochorial placentation (86). Since the trophoblast appears to be intrinsically invasive in mammals (11), apposition, adhesion, and invasion processes are thought to be controlled by the endometrium (83). In mammalian species presenting an invasive implantation, decidua restrains the invasion of the embryo in a spatiotemporal manner (20). The expression and the regulation of some factors involved in the apposition, adhesion, and invasion aspects of implantation have been reported in ruminants (62, 79), but, overall, the comparative cascade of molecular mechanisms remains largely unknown.The sequence of events occ...