Temporal changes in uterine activity and prostaglandin response to RU486 in rhesus macaques in late gestation.
Progesterone withdrawal as a mechanism of parturition in primates is controversial because maternal, fetal, and amniotic fluid progesterone concentrations do not decrease before parturition. We therefore studied the effects of RU486 on uterine activity and amniotic fluid prostaglandins in four rhesus macaques implanted with amniotic fluid and maternal vascular catheters and with fetal electrocardiogram and uterine electromyogram electrodes at 119 to 124 days' gestation (term = 168 days). Uterine electromyogram, intra-amniotic pressure (hourly contraction area, mm Hg.sec/hr), and fetal electrocardiogram were monitored continuously. After a stabilization period (6 to 9 days) RU486 was administered orally (20 mg/kg/day) at 1000 hours for 3 days. Uterine activity increased from basal levels (less than 4000 mm Hg.sec/hr) 8 hours after the first dose of RU486, reaching levels of 12,000 mm Hg.sec/hr. A sustained increase in uterine activity (13,000 to 30,000 mm Hg.sec/hr) was observed for 48 hours before cesarean section with little or no cervical effacement or dilatation. Increases in amniotic fluid prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 epsilon-cycloprostaglandin E2 occurred 40 hours after the onset of increased uterine activity. In contrast, amniotic fluid prostaglandins in the control animals delivering at term (n = 4) increased 24 to 48 hours before significant increases in uterine activity occurred. Control animals but not those given RU486 demonstrated a progressive nocturnal peak in uterine activity before delivery. Progesterone receptor blockade stimulates intense preterm uterine activity but not the orderly sequence of changes in prostaglandins and cervical status observed during normal parturition.
Division of Reproductive Biology and Behavior, Oregon Regional Primate Research Center, Beaverton 97006.
G J
GJ
Haluska
F Z
FZ
Stanczyk
M J
MJ
Cook
M J
MJ
Novy
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D007751:Labor, Induced; D008253:Macaca mulatta; D015735:Mifepristone; D010120:Oxytocics; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011374:Progesterone / Q000037:antagonists & inhibitors*; D011453:Prostaglandins / Q000378:metabolism*; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*
D004963:Estrenes; D010120:Oxytocics; D011453:Prostaglandins; D015735:Mifepristone; D011374:Progesterone