Induction of murine spiral artery modification by recombinant human interferon-gamma

Functions of uterine natural killer (uNK) cells during mouse pregnancy are maintenance of decidua basalis and promotion of uterine spiral artery modification, a process that results in thin-walled, dilated, elongated arteries with lowered resistance. Murine models indicate spiral artery modifications are triggered by release of the cytokine interferon (IFN)-gamma from uNK cells. The purpose of this study was to determine if human IFN-gamma could induce structural changes in the unmodified spiral arteries found in pregnant, alymphoid (uNK-, NK-, T-, B-) mice. Spiral arteries in pregnant Rag2 null/common cytokine chain (c) gamma null mice were modified, in a dose response manner, by daily injections of rhIFN-gamma. Administration of low dose LPS did not induce morphologically recognized structural changes. These findings are key in building humanized murine models of pregnancy since they suggest Rag2 null/gammac null mice provide a bioassay system that would detect the functioning of human uNK cells under in vivo conditions.