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

Interferon tau (IFN tau) is the antiluteolytic signal produced by the conce ptus of ruminants, Intrauterine administration of recombinant ovine IFN tau suppresses expression of endometrial estrogen receptor (ER) and oxytocin r eceptor (OTR) in the luminal and superficial glandular epithelia to abrogat e the production of luteolytic prostaglandin F-2 alpha (PGF(2 alpha)) pulse s. Subcutaneous (s.c.) injections of recombinant ovine (o) IFN tau appear t o extend the interestrous interval by altering uterine PGF(2 alpha) respons e to oxytocin. The present study tested the hypothesis that antiluteolytic effects of roIFN tau injected into the uterine lumen (paracrine) or s.c. (e ndocrine) are equivalent in suppressing expression of endometrial ER and OT R and inducing uterine expression of type I IFN-regulated Mx and ubiquitin cross-reactive proteins (UCRP). Sixteen cyclic ewes were fitted with uterin e catheters on Day 5 (Day 0 = estrus), were assigned randomly to receive tr eatment with control proteins or roIFN tau (2 x 10(7) antiviral units/day) by either intrauterine or s.c. injections from Days 11 to 15, and were ovar iohysterectomized on Day 16, Results indicated that expression of ER and OT R mRNAs in endometrial epithelium was suppressed by intrauterine but not by s.c, injections of roIFN tau. Intrauterine injections of roIFN tau increas ed expression of Mx and UCRP mRNA in the endometrium. Subcutaneous injectio ns of roIFN tau increased endometrial Mx mRNA levels but not UCRP mRNA. Une xpectedly, intrauterine and s.c. injections of roIFN tau were equally effec tive in inducing expression of Mx and UCRP mRNA in the corpus luteum. Altho ugh s.c. injections of oIFN tau induced Mx mRNA in the endometrial epitheli um, s.c. injections of roIFN tau did not abrogate activation of the uterine luteolytic mechanism by suppressing epithelial ER and OTR expression. Ther efore, results of this study failed to support the assumption that endocrin e roIFN tau mimics antiluteolytic effects of paracrine IFN tau to improve p regnancy rates in sheep.