Mechanisms for the establishment and maintenance of pregnancy: synergies from scientific collaborations.

Research on the functions of interferon tau (IFNT) led to the theory of pregnancy recognition signaling in ruminant species. But IFNT does much more as it induces expression of interferon regulatory factor 2 (IRF2) in uterine luminal (LE), superficial glandular (sGE), but not glandular (GE) epithelia. First, IRF2 silences transcription of the estrogen receptor alpha gene and, indirectly, transcription of the oxytocin receptor gene to abrogate development of the luteolytic mechanism to prevent regression of the corpus luteum and its production of progesterone for establishing and maintaining pregnancy. Second, IRF2 silences expression of classical interferon-stimulated genes in uterine LE and sGE; however, uterine LE and sGE respond to progesterone (P4) and IFNT to increase expression of genes for transport of nutrients into the uterine lumen such as amino acids and glucose. Other genes expressed by uterine LE and sGE encode for adhesion molecules such as galectin 15, cathepsins, and cystatins for tissue remodeling, and hypoxia-inducible factor relevant to angiogenesis and survival of blastocysts in a hypoxic environment. IFNT is also key to a servomechanism that allows uterine epithelia, particularly GE, to proliferate and to express genes in response to placental lactogen and placental growth hormone in sheep. The roles of secreted phosphoprotein 1 are also discussed regarding its role in implantation in sheep and pigs, as well as its stimulation of expression of mechanistic target of rapamycin mRNA and protein which is central to proliferation, migration, and gene expression in the trophectoderm cells.