Recombinant ovine and bovine interferons tau regulate prostaglandin production and oxytocin response in cultured bovine endometrial cells.

At the time of recognition of pregnancy, the bovine conceptus (embryo and associated membranes) must produce a signal that will prevent luteolysis otherwise induced by pulsatile release of prostaglandin (PG) F2alpha from the uterus in response to oxytocin (OT). In ruminants, trophoblastic interferon tau (IFN-tau) released by the conceptus appears to be the most likely candidate to trigger the establishment of pregnancy. We have compared the effect of recombinant (r) ovine (o) and bovine (b) IFN-tau on PG production, using a fully characterized model of cultured endometrial cells. In uterine epithelial cells, the production of PGF2alpha was stimulated 7.1-fold (p < 0.0001) and that of PGE2 89.0-fold (p < 0.0001) by rbIFN-tau, and 3.6-fold and 29-fold, respectively, by roIFN-tau. The stimulation resulted in a net increase in the PGE2:PGF2alpha ratio of 7.7 with rbIFN-tau and 5.1 with roIFN-tau at the optimal concentration of 1 microg/ml (p < 0.0001). By contrast, addition of OT (100 nM) alone resulted in a decrease of the PGE2:PGF2alpha ratio. The level of stimulation of PGE2 by IFN-tau was reduced in the presence of OT, showing that there was some interaction between OT and IFN-tau at the cellular level in the regulation of PG production. In uterine stromal cells, roIFN-tau and rbIFN-tau stimulated PGE2 and PGF2alpha production 12-fold (p < 0.0001). The ratio of PGE2:PGF2alpha was not affected in a dose-dependent manner, but was increased (p < 0.001) at a single dose of rbIFN-tau (0.001 microg/ml) and roIFN-tau (0.01 microg/ml). The results indicate that 1) bovine endometrial cells are more responsive to rbIFN-tau than to roIFN-tau, 2) rIFN-tau regulates PGs by stimulating PGE2 preferentially, and 3) rIFN-tau transforms the response to OT from stimulation of PGF2alpha to stimulation of PGE2.