Administration of recombinant bovine interferon-α(I) at the time of maternal recognition of pregnancy inhibits prostaglandin F(2α) secretion and causes luteal maintenance in cyclic ewes

Abstract

The antiluteolytic protein, ovine trophoblast protein-l, which is secreted by sheep embryos at about the time of the maternal recognition of pregnancy, exhibits significant structural homology with alpha interferons. Experiments were conducted to examine the effects of intra-uterine and systemic administration of a recombinant bovine interferon-α(I) (rboIFN-α(I)) upon the interoestrus interval, endometrial oxytocin receptor concentrations and secretion of prostaglandin (PG) F(2α) in cyclic ewes. In Expt 1, each ewe had a cannula placed in the tip of a uterine horn ipsilateral to a corpus luteum, 7 days after an induced oestrus. From day 9 after oestrus until day 19, ewes received either 200 (n = 4), 667 (n = 5) or 2000 (n = 9) μg/24h of rboIFN-α(I) meclofenamic acid (n = 4) or vehicle (n = 11). Other ewes received 2000 μg rboIFN-α(I) 24 h (n = 5) between days 12 and 15 only. All ewes were killed on day 19. Mean luteal phase, as determined by daily plasma progesterone measurements, was significantly longer (P < 0.01) and mean concentrations of 13,14-dihydro-15-keto PGF(2α) (PGFM) in plasma were lower (P < 0.05) in ewes receiving 667 or 2000 μg rboIFN-α(I), between days 9 and 19, or 2000 μg between days 12 and 15, than in animals from other treatment or control groups. A similar protocol was used in Expt 2, in which further ewes received either 2000 μg rboIFN-α(I) 24h (n = 5) or vehicle (n = 5) by bolus infusions twice a day into one uterine horn. Mean luteal phase was significantly (P < 0.05) longer in treated than in control animals, but differences in PGFM concentrations were not significant. In Expt 3, after a synchronized oestrus, ewes received either 2.5 mg rboIFN-α(I) by i.m. injection twice a day between days 12 and 15 (n = 10), 2.5 mg rboIFN-α(I) by i.m. injection twice a day between days 9 and 15 (n = 11), i.m. injection of vehicle alone twice a day (n = 20), or continual intra-uterine infusion of 2 mg rboIFN-α(I)/day between days 12 and 15 (n = 7). The mean luteal phase of ewes receiving rboIFN-α(I) by intrauterine infusion or i.m. injection between days 9 and 15 was significantly longer than for animals from the other two groups (P < 0.05). Concentrations of PGFM in plasma and concentrations of endometrial oxytocin receptors were significantly (P < 0.05) lower in ewes with prolonged luteal function than in the other animals. These results indicate that, when administered by either the intra-uterine or systemic routes, rboIFN-α(I) can act as an antiluteolysin, apparently by inducing changes analogous to those reported elsewhere for ovine trophoblast protein-1.