Local action of trophoblast interferons in suppression of the development of oxytocin and oestradiol receptors in ovine endometrium

Authors

G. E. Lamming, University of Nottingham
D. C. Wathes, Royal Veterinary College, London
A. P. F. Flint, University of Nottingham
J. H. Payne, University of Nottingham
K. R. Stevenson, Royal Veterinary College, London
J. L. Vallet, USDA-ARS

Date of this Version

1995

Comments

Published in Journal of Reproduction and Fertility (1995) 105, 165-175

Abstract

Luteolysis in sheep is associated with uterine secretion of pulses of prostaglandin F_2α(PGF_2α) due to the action of luteal oxytocin on endometrial oxytocin receptors. For pregnancy to become established inhibition of oxytocin receptors is important as an antiluteolytic mechanism. The maternal recognition of pregnancy in cattle and sheep involves production, by the trophoblast, of a type 1 interferon (IFN-τ)that suppresses uterine development of oxytocin receptors and the generation of luteolytic episodes of PGF_2α. The action of IFN-τ in surgically prepared unilaterally pregnant ewes was investigated. Finn-Dorset ewes were anaesthetized on day 6 or 7 of the oestrous cycle and one uterine horn was surgically isolated at the uterine bifurcation from the body of the uterus. Ewes were mated at the subsequent oestrus 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 measurable uterine IFN-τ but there were high concentrations of oxytocin receptors in both horns. In the pregnant ewes, on day 16 after mating, the oxytocin receptor concentration was 45 ± 11 fmol mg^-1 protein in the pregnant horn and 585 ± 131 fmol mg^-1 in the non-pregnant horn. Antiviral activity was 5.8 ×10⁷ ± 5.2 ×10⁷ U ml^-1 in the pregnant horn and 2.9×10³±1.2 ×10³ U ml^-1in 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-τ and high oxytocin receptor concentrations in the isolated horn equivalent to those expected at the onset of luteolysis. In situ hybridization to ovine mRNA encoding the oxytocin receptor and autoradiographic studies using the ¹²⁵I-labelled oxytocin antagonist d(CH₂)₅[Tyr(Me)²,Thr⁴,Tyr-NH₂⁹]-vasotocin both showed that the large amount of oxytocin receptor message and binding sites in the endometrium of the isolated horn were localized in the luminal epithelium. Immunocytochemical studies showed that there was a suppression of oestradiol receptors in the pregnant horn but high concentrations equivalent to those at oestrus were present in the isolated horn. The content of progesterone receptors was low in the stromal tissue only in both horns, a pattern of localization similar to that seen in the late luteal phase and in early pregnancy. These results are consistent with a local action of IFN-τ on endometrial oxytocin receptors and endometrial oestrogen receptors; they raise the possibility that reduced oestrogen receptor function mediates the inhibitory effect of IFN-τ on oxytocin receptor expression, but the exact relationship between the suppression of oestradiol and oxytocin receptors in relation to the antiluteolytic action of IFN-τ requires further study.