Differential effects of intrauterine and subcutaneous administration of recombinant ovine interferon tau on the endometrium of cyclic ewes

Abstract

Interferon tau (IFNτ) is the antiluteolytic signal produced by the conceptus of ruminants. Intrauterine administration of recombinant ovine IFNτ suppresses expression of endometrial estrogen receptor (ER) and oxytocin receptor (OTR) in the luminal and superficial glandular epithelia to abrogate the production of luteolytic prostaglandin F(2α) (PGF(2α)) pulses. Subcutaneous (s.c.) injections of recombinant ovine (o) IFNτ appear to extend the interestrous interval by altering uterine PGF(2α) response to oxytocin. The present study tested the hypothesis that antiluteolytic effects of roIFNτ injected into the uterine lumen (paracrine) or s.c. (endocrine) are equivalent in suppressing expression of endometrial ER and OTR and inducing uterine expression of type 1 IFN-regulated Mx and ubiquitin cross- reactive proteins (UCRP). Sixteen cyclic ewes were fitted with uterine catheters on Day 5 (Day 0 = estrus), were assigned randomly to receive treatment with control proteins or roIFNτ (2 x 107 antiviral units/day) by either intrauterine or s.c. injections from Days 11 to 15, and were ovariohysterectomized on Day 16. Results indicated that expression of ER and OTR mRNAs in endometrial epithelium was suppressed by intrauterine but not by s.c. injections of roIFNτ. Intrauterine injections of roIFNτ increased expression of Mx and UCRP mRNA in the endometrium. Subcutaneous injections of roIFNτ increased endometrial Mx mRNA levels but not UCRP mRNA. Unexpectedly, intrauterine and s.c. injections of roIFNτ were equally effective in inducing expression of Mx and UCRP mRNA in the corpus luteum. Although s.c. injections of roIFNτ induced Mx mRNA in the endometrial epithelium, s.c. injections of roIFNτ did not abrogate activation of the uterine luteolytic mechanism by suppressing epithelial ER and OTR expression. Therefore, results of this study failed to support the assumption that endocrine roIFNτ mimics antiluteolytic effects of paracrine IFNτ to improve pregnancy rates in sheep.