The History of Interferon-Stimulated Genes (ISGs) in Pregnant Cattle, Sheep, and Pigs.

Abstract

Expression of the classical interferon (IFN) stimulated genes (ISGs) increases in the endometrial stroma and glandular epithelium (GE) through activation of signal transducer and activator of transcription (STAT) signaling in response to the secretion of IFN tau (IFNT) and IFN gamma (IFNG) by the conceptuses of ruminants, including cattle and sheep, and pigs respectively. The first of the classical ISGs to be characterized was ISG15 in cattle. Classical ISGs are not expressed by the endometrial luminal epithelium (LE) due to the expression of interferon regulatory factor 2 (IRF2) in the LE that prevents expression of ISGs in the LE. Classical ISG expression in the endometrium serves as a reliable indicator of conceptus health and elongation in cattle. There are also nonclassical ISGs that are upregulated in endometrial LE in response to progesterone (P4) that and are further stimulated by IFNT in sheep, the intracellular signaling pathway responsible for IFN effects on expression is unknown. ISGs are also upregulated in extrauterine tissues including CL and peripheral blood mononuclear cells (PBMCs). Expression of ISGs by the PBMCs of cattle serve as an early prognosticator of pregnancy. The physiological roles of ISGs remain obscure, but evidence suggests that they are at least in part involved in modifying the immune system to support endometrial remodeling necessary for successful implantation of the conceptus. Our understanding of these ISGs is primarily the result of work from the laboratories of Drs. Fuller Bazer, Thomas (Tod) Hansen, Gregory Johnson, Hakhyun Ka, Patrick Lonergan, Troy Ott, and Thomas Spencer.