LOCAL-ACTION OF TROPHOBLAST INTERFERONS IN SUPPRESSION OF THE DEVELOPMENT OF OXYTOCIN AND ESTRADIOL RECEPTORS IN OVINE ENDOMETRIUM

Luteolysis in sheep is associated with uterine secretion of pulses of prostaglandin F-2 alpha (PGF(2 alpha)) due to the action of luteal oxy tocin on endometrial oxytocin receptors. For pregnancy to become estab lished inhibition of oxytocin receptors is important as an antiluteoly tic mechanism. The maternal recognition of pregnancy in cattle and she ep involves production, by the trophoblast, of a type 1 interferon (IF N-tau) that suppresses uterine development of oxytocin receptors and t he generation of luteolytic episodes of PGF,,. The action of IFN-tau i n surgically prepared unilaterally pregnant ewes was investigated. Fin n-Dorset ewes were anaesthetized on day 6 or 7 of the oestrous cycle a nd one uterine horn was surgically isolated at the uterine bifurcation from the body of the uterus. Ewes were mated at the subsequent oestru s either by a fertile or by a vasectomized ram and killed on day 13 or 16 after mating. On day 16, in the non-pregnant ewes, there was no me asurable uterine IFN-tau but there were high concentrations of oxytoci n receptors in both horns. In the pregnant ewes, on day 16 after matin g, the oxytocin receptor concentration was 45 +/- 11 fmol mg(-1) prote in in the pregnant horn and 585 +/- 131 fmol mg(-1) in the non-pregnan t hem. Antiviral activity was 5.8 x 10(7) +/- 5.2 x 10(7) U ml(-1) in the pregnant horn and 2.9 x 10(3) +/- 1.2 x 10(3) U ml(-1) in the non- pregnant horn. Thus, 16 days after mating, the pregnant horn exhibited high antiviral activity but oxytocin receptors were suppressed, while in the same endocrine environment (characteristic of pregnancy) there were low IFN-tau and high oxytocin receptor concentrations in the iso lated horn equivalent to those expected at the onset of luteolysis. In situ hybridization to ovine mRNA encoding the oxytocin receptor and a utoradiographic studies using the I-125-labelled oxytocin antagonist d (CH2)(5)[Tyr(Me)(2),Thr(4),Tyr-NH29]-vasotocin both showed that the la rge amount of oxytocin receptor message and binding sites in the endom etrium of the isolated horn were localized in the luminal epithelium. Immunocytochemical studies showed that there was a suppression of oest radiol receptors in the pregnant horn but high concentrations equivale nt to those at oestrus were present in the isolated hem. The content o f progesterone receptors was low in the stromal tissue only in both he ms, a pattern of localization similar to that seen in the late luteal phase and in early pregnancy. These results are consistent with a loca l action of IFN-tau on endometrial oxytocin receptors and endometrial oestrogen receptors; they raise the possibility that reduced oestrogen receptor function mediates the inhibitory effect of IFN-tau on oxytoc in receptor expression, but the exact relationship between the suppres sion of oestradiol and oxytocin receptors in relation to the antiluteo lytic action of IFN-tau requires further study.