Pregnancy recognition in ruminants, pigs and horses: Signals from the trophoblast

Interferon tau (IFNτ), secreted by trophectoderm of sheep, cow and goat conceptuses (embryo and associated membranes), is the pregnancy recognition signal. The 172 AA mature IFNτ protein with conserved cysteine residues at positions 1, 29, 99 and 139 is a unique and largely uncharacterized subclass of Type I interferon. Interferon tau, the paracrine antiluteolytic signal, acts on uterine epithelium to prevent pulsatile release of PGF2α and insure maintenance of a functional corpus luteum. Secretion of IFNτ is limited to early pregnancy, with Days 12-13 for sheep and Days 14-17 for cows and goats being critical for pregnancy recognition. Secretion of ovine (o) IFNτ is stimulated by granulocyte monocyte/macrophage colony stimulating factor (GM-CSF) or insulin-like growth factors I and II combined suggesting that uterine factors influence IFNτ gene expression. There are few uterine receptors for oxytocin (OTR) or estrogen (ER) in early pregnant ewes or after intrauterine injections of oIFNτ, so pulsatile release of PGF required for luteolysis is abrogated. Ovine IFNτ may stabilize progesterone receptors (PR) to inhibit up-regulation of ER and OTR in uterine epithelium to prevent luteolysis; an effect likely mediated by IFN-stimulated response elements in the receptor genomic DNA. Pig conceptuses secrete both IFNα (25%) and IFNγ (75%) between Days 15 and 21 of gestation, but their roles in early pregnancy are unknown. Inhibition of secretion of luteolytic PGF in pigs is in response to estrogens of blastocyst origin which induce upregulation of endometrial receptors for prolactin. Effects of prolactin and estrogen may be influenced by IFNα and/or IFNγ from pig trophoblast. The equine conceptus may signal pregnancy recognition through secretion of a low molecular weight protein, estrogen and/or PGE, but the precise signal and its mechanism of action have not been elucidated.