Nature and possible functions of interferons secreted by the preimplantation pig blastocyst

In several ungulate species, the preimplantation trophoblast, among various secretions, produces large amounts of antiviral activity that was identified as interferon (IFN). IFNs (types I and II) are pleiotropic cytokines, which in addition to a potent antiviral activity, exert multiple effects on cell growth and differentiation, in particular on the cells of the immune system. In ruminants, trophoblastic IFN, or trophoblast protein-1 (TP-1), was found to consist of a multigenic family related to type I IFN-omega. These IFNs exert hormone-like effects through receptors present on the endometrium, leading to the prolongation of luteal life-span and hence to sustained progesterone secretion. In pigs, a species in which the maternal recognition of pregnancy is controlled by conceptus-derived oestrogens, two IFNs have been found in the preimplantation trophoblast. The major species is IFN-gamma (type II), that so far had been found only in activated T lymphocytes and natural killer (NK) cells. Transcription of the IFN-gamma gene in the pig trophoblast differs from that in mature lymphocytes, since two mRNAs are present. The other component with antiviral activity is a novel type I IFN, distant in sequence from IFN-alpha, beta, omega, and containing seven cysteines in its deduced mature protein. These two unrelated IFNs are temporally co-induced, with maximal secretion at day 16 of pregnancy. Specific receptors for both IFNs have been found on endometrial epithelial cells, but not on the preimplantation trophoblast, suggesting a paracrine effect on the uterus. Different hypotheses as to their role(s) in the establishment or maintenance of implantation are discussed. Whereas an indirect anti-infectious (antiviral) protection of the conceptus by IFNs cannot be ruled out, arguments are presented that do not favour a role in the immune tolerance of the conceptus.