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This version published online on December 6, 2007
Endocrinology, doi:10.1210/en.2007-0863
A more recent version of this article appeared on March 1, 2008
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Submitted on June 27, 2007
Accepted on November 29, 2007

Expression of ISGs in extrauterine tissues during early pregnancy in sheep is the consequence of endocrine IFN-{tau} release from the uterine vein

João F. Oliveira, Luiz E. Henkes, Ryan L. Ashley, Scott H. Purcell, Natalia P. Smirnova, D. N. Rao Veeramachaneni, Russell V. Anthony, and 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, CO 80523, USA; BioRep, Departamento de Clínica de Grandes Animais, Centro de Ciências Rurais, Universidade Federal de Santa Maria, 97105–900, Santa Maria, RS, Brazil

* To whom correspondence should be addressed. E-mail: thomas.hansen{at}colostate.edu.

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






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