A pilot study on the influence of early pregnancy interferon τ to the expression of IGF-binding proteins in primary bovine hepatocytes

The implantation period is crucial for the establishment of pregnancies in cows. Interferon τ (IFNτ) is produced during early implantation and acts in autocrine, paracrine and endocrine fashions on other endocrine systems. One of these is the insulin-like growth factor 1 (IGF-1) system, which is important for cell growth, proliferation, and therefore pregnancy establishment. This study investigated the effect of IFNτ on the expression of hepatic IGF-binding proteins (IGFBPs) in vitro. Primary bovine hepatocytes in a 2D sandwich culture model were stimulated with recombinant bovine IFNτ (rbIFNτ; 0.1-10.0 ng/mL) for six hours. The mRNA expression of IGFBP-1 to -7 and acid labile subunit (ALS) was measured using qRT‒PCR, and protein production was confirmed using western ligand blotting. All the IGFBPs (1-7) and ALS were expressed at basal levels in primary bovine hepatocytes, with IGFBP-2 to -4 secreted at appreciable concentrations in the medium. The expression of IGFBP-2 to -6 was stimulated by IFNτ, (treatment with rbIFNτ vs. control; IGFBP-2: for 0.5 ng/mL rbIFNτ, p = 0.0166; IGFBP-3: for 0.5 ng/mL, 5.0 ng/mL, and 10.0 ng/mL rbIFNτ, p = 0.0293, p = 0.0252, and p = 0.0099; IGFBP-4: for 0.5 ng/mL rbIFNτ, p = 0.0024; IGFBP-5: for 0.5 ng/mL and 10 ng/mL rbIFNτ, p = 0.0008 and p = 0.0421; IGFBP-6: for 0.1-10.0 ng/mL rbIFNτ, p = 0.0498-0.0022). These results indicate modulation of the IGF-system through IFNτ, which may contribute to adaptations supporting the early establishment of pregnancies in cattle.