Interferons as Hormones of Pregnancy

About 5 yr ago it was discovered that a protein which was secreted in quantity by preimplantation sheep conceptuses and implicated in preventing luteolysis during the second and third weeks of pregnancy was, in fact, structurally related to type I interferons (IFN), proteins best known for their antiviral and immunomodulatory activities. This discovery attracted considerable attention because it revealed a new and completely unsuspected role for a cytokine as a reproductive hormone. Several reviews have been published on various aspects of this topic (1–10). In the more comprehensive updated article that follows, we describe how IFN came to be implicated as antiluteolytic agents in domestic ruminant species, the properties of these IFN, and some of the unusual features pertaining to their expression and transcriptional regulation. We address the questions as to whether these IFN have any unique biological and structural properties, as to how they evolved, and as to whether type I IFN in general might have a universal role in mammalian pregnancy