Abstract. 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. Key words: Estrous cycle, Gene expression, Pregnancy, Progesterone (J. Reprod. Dev. 58: [189][190][191][192][193][194][195] 2012) I n cattle, as in other ungulate ruminants, the implantation process is characterized by a protracted period of elongation of the hatched blastocyst followed by apposition, attachment and adhesion of the trophectoderm to the uterine luminal epithelium (LE) [1,2]. Following successful fertilisation of an oocyte in the oviduct, the resulting embryo enters the uterus on approximately day 4 of pregnancy where it undergoes a number of cell divisions to form the morula which, after further differentiation, forms a blastocyst consisting of the inner cells mass (which will eventually give rise to the embryo/foetus) and an outer cell mass consisting of trophectoderm cells which ultimately give rise to the placenta. Up to the blastocyst stage of development, the embryo is relatively autonomous i.e. contact with the maternal uterine environment is not strictly required, as evidenced by the fact it is possible to culture embryos in vitro up to the blastocyst stage of development. However, once the embryo hatches from the zona pellucida (approximately day 9-10), significant morphological changes occur in the conceptus of domestic animals, including cattle, that differentiate the early pregnancy events from those of rodents, humans and non-human primates. The hatch...