Maintenance of secretion of progesterone from the ovarian corpus luteum (CL) is essential for establishment of pregnancy in cows. The luteolytic prostaglandin (PG) is PGF2ot in cows causing regression of the corpus luteum and cessation of progesterone production. Pregnancy is established and maintained through a complex interaction between the conceptus and the maternal environment including the uterus and corpus luteum. This complex interaction was found to be driven by trophoblastic proteins. A specific trophoblastic protein was determined to have homology with interferons and later identified as interferon-tau (IFN-t). One function of IFN-t is to extend the lifespan of corpus luteum and to reduce the pulsatile release of PGF2ct from the endometrium in cows. A clear inhibition of secretion of PGF2ft by IFN-t in vitro from bovine endometrial cells has been shown by a number of studies. However, the cellular mechanisms as to how PGF2a secretion is inhibited by trophoblastic IFN-t have been under extensive investigation. Studies over the years have suggested various regulatory mechanisms as to how IFN-t exerts its effect to reduce PGF2a secretion to maintain the corpus luteum. Current explanations are that IFN-t acts on the endometrium to reduce expression of estrogen receptor alpha (ERa) and oxytocin receptor (OTR) that are involved directly in stimulating pulsatile PGF2a secretion from uterine epithelial cells. Alternatively, IFN-t acts on uterine epithelial cells to cause transcriptional inactivation of the PG H Synthase-2 (PGHS-2) gene.