Effect of injected bovine interferon- I1 on oestrous cycle length and pregnancy success in sheep

Abstract

In Exp. 1 twice daily i.m. injections of 2 mg recombinant bovine IFN-alpha I1 (rboIFN-alpha I1) (N = 24) or placebo (N = 25) were administered to ewes from Day 12 to Day 16 during a normal oestrous cycle. Treatment did not increase (P greater than 0.10) oestrous cycle length (20.7 +/- 1.2 versus 18.5 +/- 1.4 days). In Exp. 2, ewes were injected twice daily with 2 mg IFN (N = 34) or placebo (N = 36) from Days 11 to 18 after natural mating. The rboIFN-alpha I1 significantly (P = 0.05) improved pregnancy rate (79% versus 58%) as determined by a failure of ewes to return to oestrus within 50 days. The number of ewes that lambed was greatest in the rboIFN-alpha I1-treatment group (71% versus 50%; P = 0.07), and no teratogenic effects were observed in the young born to IFN-treated ewes. The study was repeated a second year with a more fecund group of ewes (Exp. 3). More (P = 0.08) ewes injected with rboIFN-alpha I1 (58/65) than placebo-treated ewes (48/61) were judged pregnant by ultrasound. Again more ewes lambed (55 versus 45) and more lambs were born (98 versus 80) from the rboIFN-alpha I1-treated group. Combining the data from both studies revealed a significant (P = 0.01) effect of treatment. The amount of antiviral activity in jugular vein blood of ewes injected with rboIFN-alpha I1 (2 mg) was determined over time in Exp. 4. Activity rose to a maximum (approximately 450 IRU/ml) within 1-2 h and declined by over 75% in 24 h. Single injections of 1, 2 and 5 mg in buffer or 2 mg emulsified in sesame oil all gave similar profiles of antiviral activity in jugular blood over a 48-h period. In Exp. 5, antiviral activity was measured in uterine vein, ovarian artery and jugular vein serum of untreated pregnant (N = 7) and non-pregnant (N = 11) ewes at Day 15 after mating. Activity was detected in the uterine vein (58 +/- 19 IRU/ml) of all pregnant ewes. The observations in Exps 1-5 are consistent with a role for conceptus-derived IFN-alpha in maternal recognition of pregnancy and suggest that supplemental IFN-alpha might be useful in improving pregnancy success in sheep.

Trophoblast interferon and pregnancy

“…Attempts to use IFN-α or IFN-τ to improve pregnancy rates have been inconclusive; Nephew et al (1990) and Schalue-Francis et al (1991) both showed that IFN-α treatment increased lambing rate after natural mating, but the study of SchalueFrancis et al (1991) could not be repeated with a group of animals with more normal fertility. Systemic administration of IFN-α decreased pregnancy rates in heifers, possibly due to the decrease in serum concentration of progesterone seen in this species after IFN-α administration (Barros et al, 1992) but IFN-τ improved calving rates in red deer after asynchronous embryo transfer (Demmers et al, 2000).…”

Pharmacokinetics of Interferon-Alpha in Pregnant Women and Fetoplacental Passage

“…Intramuscular injec tion of bovine recombinant IFN-a between the 12th and 16th day of gestation increases embryo survival in sheep [6], Shalue-Francis et al [7] obtained similar results in this spe cies and observed no teratogenic effect. How ever, Barros et al [8] found that bovine IFN-a injections in inseminated heifers considerably reduced the percentage of gestation.…”

Luteal function after intrauterine infusion of recombinant bovine interferon- I1 into postpartum beef cows expected to have short or normal luteal phases

“…Similarly, Hunter et al (1989) have demonstrated an association between pulses of oxytocin and PGFM on day 5 in ewes with short luteal phases similar to that observed during normal luteolysis. In addition, Zollers et al (1991a) (Plante et al, 1988;Thatcher et al, 1989) and sheep (Stewart et al, 1989;Schalue-Francis et al, 1991) anticipated to have normal luteal phases. Similarly, luteolysis is delayed in sheep and cattle following intrauterine infusion of oTP-1 or bovine conceptus proteins (Knickerbocker et al, 1986;Vallet el al, 1988;Thatcher et al, 1989).…”