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.
OBJECTIVE
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 E(2). 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 microg/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.
Ma
X H
XH
Laboratory of Pregnancy and Newborn Research, Department of Biomedical Sciences, College of Veterinary Medicine, Ithaca, NY 14853-6401, USA.
Wu
W X
WX
Brenna
J T
JT
Nathanielsz
P W
PW
D000818:Animals; D001623:Betamethasone; D002585:Cesarean Section; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007751:Labor, Induced; D009215:Myometrium / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018045:Receptors, Oxytocin / Q000235:genetics*; D012756:Sheep; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D007527:Isoenzymes; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D001623:Betamethasone; D011451:Prostaglandin-Endoperoxide Synthases