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 betamethaso ne-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 prost aglandin E-2. To valuate the mechanism of inhibition of prostaglandin produ ction and delay of onset of labor and time of delivery in PUFA-treated shee p, we determined the effect of PUFA on myometrial prostaglandin H synthase (PGHS) 1 and 2 and oxytocin receptor mRNA levels in betamethasone-induced l abor. 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) intravenou sly (IV) to the ewe. At 125 days' gestation, betamethasone was administered IV (10 mu g/h over 48 hours) to fetuses of both intralipid- and PUFA-treat ed ewes. Myometrium was collected at necropsy either during betamethasone-i nduced labor as evaluated by myometrial electromyography or within 5 days o f the termination of betamethasone infusion, if delivery did not occur afte r fetal betamethasone infusion. Total myometrial RNA was analyzed by Northe rn blot for oxytocin receptor and PGHS1 and 2 mRNA normalized for 18s. RESULTS: Treatment with PUFA decreased myometrial PGHS2 mRNA but did not al ter myometrial PGHS1 and oxytocin receptor PUFA decreased myometrial PGHS2 mRNA but did not alter myometrial PGHS1 nd oxytocin receptor mRNA after bet amethasone administration. CONCLUSIONS: This finding provides a mechanism whereby PUFA delays betameth asone-induced delivery in sheep and suggests a potential role of PUFA as an effective tocolytic agent in human pregnancy. (J Soc. Gynecol Investig 200 0;7:233-7) Copyright (C) 2000 by the Society for Gynecologic Investigation.