In cattle, the majority of pregnancy loss can be attributed to early embryonic loss which occurs prior maternal recognition of pregnancy on Day 16 (Day 0 = ovulation). During this time, carefully orchestrated spatio-temporal alterations in the transcriptomic profile of the endometrium are required to drive conceptus elongation, via secretions from the endometrium (termed histotroph) and establish uterine receptivity to implantation. The two main modulators of these processed are progesterone (P4) and the pregnancy recognition signal interferon tau (IFNT). Altered concentrations of P4 in circulation mediate its effects via the endometrium and have been associated with different rates of conceptus elongation in cattle. Transcriptomic analysis of the endometrium has shown that modulation of circulating P4 alters endometrial expression of genes that can contribute to histotroph composition, which is beneficial (when P4 is supplemented) or detrimental (when P4 is reduced) to the developing conceptus. In addition, down-regulation of the progesterone receptor, required to establish uterine receptivity, is altered in the endometrium of heifers with altered P4 concentrations. IFNT, a type 1 interferon, also significantly impacts on the endometrial transcriptome. It induces the expression of a large number of classical interferon stimulated genes as early as Day 15 of pregnancy. In summary, the successful establishment of pregnancy in cattle requires a sequence of key events to ensure appropriate maternally derived secretions, establish uterine receptivity to implantation as well as an adequate endometrial response to IFNT production.