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Expression of Interferon (IFN)-Stimulated Genes in Extrauterine Tissues during Early Pregnancy in Sheep Is the Consequence of Endocrine IFN- Release from the Uterine Vein

Animal Reproduction and Biotechnology Laboratory (J.F.O., L.E.H., R.L.A., S.H.P., N.P.S., D.N.R.V., R.V.A., T.R.H.), Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523; and BioRep (J.F.O.), Departamento de Clínica de Grandes Animais, Centro de Ciências Rurais, Universidade Federal de Santa Maria 97105-900, Santa Maria, Rio Grande do Sul, Brazil

Address all correspondence and requests for reprints to: Dr. Thomas R. Hansen, Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Campus Delivery 1683, Fort Collins, Colorado 80523. E-mail: thomas.hansen{at}colostate.edu.

The ruminant conceptus synthesizes and secretes interferon (IFN)-, which presumably acts via an intrauterine paracrine mechanism to signal maternal recognition of pregnancy. The aims of this study were to determine whether IFN-stimulated genes (ISG) such as ISG15 and OAS-1 are differentially expressed in blood cells circulating in the uterus of ewes; whether extrauterine components of the reproductive tract such as the corpus luteum (CL) also express mRNA for these ISG, and whether antiviral activity is greater in uterine vein than in uterine artery during early pregnancy. The concentrations of mRNA for both ISG were significantly greater (P < 0.0001) in endometrium and jugular blood of 15-d pregnant ewes than in nonpregnant ewes. ISG15 and OAS-1 mRNA concentrations were also greater (P < 0.05) in CL from 15-d pregnant ewes than in nonpregnant ewes. Immunohistochemistry revealed intense staining for ISG15 in large luteal cells on d 15 of pregnancy. Blood cells from uterine artery and vein of 15-d pregnant ewes had similar ISG15 and OAS-1 mRNA concentrations, suggesting that these cells were not conditioned by IFN- within the uterus. By using an antiviral assay, uterine venous blood was found to contain 500- to 1000-fold higher concentrations of bioactive IFN- than in uterine arterial blood on d 15 of pregnancy. It is concluded that uterine vein releases IFN-, which induces ISG in extrauterine tissues such as the CL during the time of maternal recognition of pregnancy.