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Effect of Interferon- Administration on Endometrium of Nonpregnant Ewes: A Comparison with Pregnant Ewes

Departments of Animal Sciences (Y.C., J.A.G., E.A., A.M.W., R.M.R.), Biochemistry (R.M.R.), Statistics (L.B.H.), and Biomedical Sciences (C.S.R.), University of Missouri, Columbia, Missouri 65211; Department of Animal Sciences (A.D.E.), University of Florida, Gainesville, Florida 32611; Monsanto Company (N.P.), St. Louis, Missouri 63167; and Atwater-Merced Veterinary Clinics (M.P.A.), Merced, California 95348

Address all correspondence and requests for reprints to: R. M. Roberts, 240b Christopher S. Bond Life Sciences Center, 1201 East Rollins Road, University of Missouri-Columbia, Columbia, Missouri 65211. E-mail: robertsrm{at}missouri.edu.

In ruminants, conceptus interferon- (IFNT) alters maternal physiology to accommodate a pregnancy. We hypothesized that the effectiveness of IFNT on extending corpus luteum (CL) life span in nonpregnant ewes would depend upon the dose and manner of administration and would 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/d); 3) saline im injection; 4) im injection of IFNT4 at low dose (200 µg/d); and 5) high dose (2 mg/d). CL life span was increased in groups 2 and 5, but not in 1, 3, and 4. Endometrial RNA extracted from groups 1–5 on d 14 and from d 14 pregnant and nonbred (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 nine down-regulated during pregnancy. Responses were slightly less in groups 2 and 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-II, hypoxia-inducible factor 1, oxytocin receptor, prostaglandin F synthase, and cyclooxygenase-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.

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