Maternal intravenous administration of long chain n-3 polyunsaturates to the pregnant ewe in late gestation results in specific inhibition of prostaglandin H synthase (PGHS) 2, but not PGHS1 and oxytocin receptor mRNA in myometrium during betamethasone-induced labor

OBJECTIVES: Both the onset of labor and time to delivery during betamethasone-induced delivery are delayed by omega-3 polyunsaturated fatty acid (PUFA) administration to pregnant sheep. That fatty acid also inhibits the labor-related increase in maternal plasma estradiol and maternal and fetal prostaglandin E₂. To evaluate the mechanism of inhibition of prostaglandin production and delay of onset of labor and time of delivery in PUFA-treated sheep, we determined the effect of PUFA on myometrial prostaglandin H synthase (PGHS) 1 and 2 and oxytocin receptor mRNA levels in betamethasone-induced labor. METHODS: At 124 days' gestation, a 20% emulsion of either intralipid (IL, n = 6) or PUFA (n = 6) was infused continuously (3 mL/kg per day) intravenously (IV) to the ewe. At 125 days' gestation, betamethasone was administered IV (10 μg/h over 48 hours) to fetuses of both intralipid- and PUFA-treated ewes. Myometrium was collected at necropsy either during betamethasone-induced labor as evaluated by myometrial electromyography or within 5 days of the termination of betamethasone infusion, if delivery did not occur after fetal betamethasone infusion. Total myometrial RNA was analyzed by Northern blot for oxytocin receptor and PGHS1 and 2 mRNA normalized for 18s. RESULTS: Treatment with PUFA decreased myometrial PGHS2 mRNA but did not alter myometrial PGHS1 and oxytocin receptor mRNA after betamethasone administration. CONCLUSIONS: This finding provides a mechanism whereby PUFA delays betamethasone-induced delivery in sheep and suggests a potential role of PUFA as an effective tocolytic agent in human pregnancy. Copyright (C) 2000 by the Society for Gynecologic Investigation.