Protective Effects of Interferon-tau Against Lipopolysaccharide-Induced Embryo Implantation Failure in Pregnant Mice.

Abstract

Interferon-tau (IFN-τ), a novel type I interferon, is produced by trophoblast cells in ruminants. Previous studies have confirmed that IFN-τ could induce immunological tolerance in humans and other species. However, there are few reports on whether IFN-τ has a protective effect on embryo implantation failure caused by excessive inflammation at the maternal-fetal interface. In our study, a mouse model of lipopolysaccharide (LPS)-induced implantation failure was successfully established, and we investigated the protective effects of IFN-τ. First, we showed that IFN-τ increased the number of implanted embryos in LPS-treated pregnant mice. Subsequently, quantitative real-time polymerase chain reaction (qPCR) and ELISA results showed that several inflammatory cytokines [IL-1β and tumor necrosis factor-alpha (TNF-α)] whose expression was upregulated by LPS were reversed by IFN-τ treatment. Furthermore, we performed Western blotting and found that IFN-τ restrained the LPS-induced phosphorylation of IκBα and NF-κB p65. Moreover, qPCR and immunohistochemistry analyses showed that IFN-τ decreased the LPS-induced expression of mouse major histocompatibility complex (MHC) class I genes (H-2K and H-2D) in LPS-treated pregnant mice. Taken together, these results suggest that IFN-τ has a protective effect in LPS-induced implantation failure by downregulating MHC class I genes expression and inhibiting the production of inflammatory cytokines.