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This version published online on February 9, 2006
Endocrinology, doi:10.1210/en.2005-1310
A more recent version of this article appeared on May 1, 2006
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Submitted on October 14, 2005
Accepted on January 31, 2006

Effect of Interferon-tau Administration on Endometrium of Non-Pregnant Ewes: a Comparison with Pregnant Ewes

Yizhen Chen, Jonathan A. Green, Eric Antoniou, Alan D. Ealy, Nagappan Mathialagan, Angela M. Walker, Mary P. Avalle, Cheryl S. Rosenfeld, Leonard B. Hearne, and R. Michael Roberts*

Department of Animal Sciences, University of Missouri, Columbia, MO 65211; Department of Animal Sciences, University of Florida, Gainesville, FL 32611; Department of Biochemistry, University of Missouri, Columbia, MO 65211; Monsanto Company, 800 North Lindbergh Blvd, St. Louis, MO 63167; Atwater-Merced Veterinary Clinics, Merced, CA 95348; Biomedical Sciences, University of Missouri, Columbia, MO 65211; Department of Statistics, University of Missouri, Columbia, MO 65211

* To whom correspondence should be addressed. E-mail: robertsrm{at}missouri.edu.

In ruminants, conceptus interferon-{tau} (IFNT) alters maternal physiology to accommodate a pregnancy. We hypothesized that the effectiveness of IFNT on extending CL lifespan in non-pregnant ewes would depend upon the dose and manner of administration and be correlated with the response in gene expression in endometrium. We anticipated that IFNT, whether administered IM or by uterine infusion, would mimic changes observed in pregnancy. Ewes were assigned to five treatments: 1) uterine infusion of saline; 2) uterine infusion of ovine IFNT4 (200 µg/day); 3) saline IM injection; 4) IM injection of IFNT4 at low (200 µg/day) and 5) high dose (2 mg/day). CL lifespan was increased in groups 2 and 5, but not in 1, 3, and 4. Endometrial RNA extracted from groups 1-5 on day 14 and from day 14 pregnant and non-bred (cyclic) ewes was used to assess expression of 70 genes on microarrays. When pregnant and cyclic ewes were compared, 30 genes were up-regulated and 9 down-regulated during pregnancy. Responses were slightly less in Group 2 and Group 5 but were much lower in Group 4. The majority of the highly up-regulated genes were associated with antiviral responses. Those down-regulated included ones for IGF-2, hypoxia-inducible factor 1{alpha}, oxytocin receptor, prostaglandin F synthase, and COX-2. Quantitative PCR for selected genes confirmed these data and revealed that similar gene expression changes occurred in the CL of pregnant and Group 2 ewes. IFNT treatment mimics pregnancy, but relatively high doses of IM-injected IFNT are required to elicit a full endometrial response.
Key words: endometrium • gene expression • hypoxia-inducible factor • IGF-2 • microarray • prostaglandin




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