DUAL MESSENGER FUNCTION FOR PROSTAGLANDIN E-2 (PGE(2)) IN HUMAN PLACENTA

There is periparturitional increase of prostaglandin E-2 (PGE(2)) in t he plasma and amniotic fluid of humans. PGE(2) increases uterine contr actions and also increases uterine blood flow to sustain the contracti ons. A question arises as to what role PGE(2) plays in human placental circulation. It may regulate fete-placental blood flow and closure of placental resistance vessels at parturition. Therefore, we have inves tigated (a) the release of PGE(2) into fetal and maternal circulations , and (b) the influence of PGE(2) on the feto-placental pressure in th e isolated perfused cotyledon of normal human term placenta. The place ntal cotyledon was perfused with aerated (21% O-2, 5% CO2) Krebs-Ringe r bicarbonate buffer (pH 7.4, 37 degrees C) containing 2% albumin on b oth maternal (230 ml, 12 ml/min., 0.6'' Hg) and fetal (93 ml, 1.75 ml/ min., 1.75'' Hg) sides in a closed recirculating system. In one group of cotyledons, perfusion samples (2 mi) were collected at regular inte rvals from both perfusates for 3 hrs. and PGE(2) was determined in ali quots (0.5 ml) of samples by a specific radioimmunoassay. In a second set of cotyledons, exogenous PGE(2) was administered into fetal perfus ate, and pressure was monitored as a function of time. These experimen ts gave the following results: 1) During the initial 20 min., a consta nt level of PGE(2) (2.3-4.4 pg/ml) was maintained in both perfusates. At 3 hrs., the concentrations increased to about 110 ng/ml on the feta l side and 30 ng/ml on the maternal side. The total amount of PGE(2) a ccumulated in the fetal and maternal reservoirs reached to 10.16 and 7 .03 ng, respectively. 2) PGE(2) (10-150 ng/ml) increased the fete-plac ental perfusion pressure in a concentration dependent manner. At 150 n g/ml, the pressure increased to 125-240% of control pressure observed at the beginning of the experiment. These studies suggest that a) plac ental trophoblast has the capacity for the synthesis and release of PG E(2) into fetal and maternal circulations; b) PGE(2) exhibits differen tial effects in the placental and uterine blood vessels, vase-constric tion in placental vessels and vasodilation in uterine blood vessels, a nd (c) PGE(2) exhibits dual effects on blood vessels possibly by activ ating two different subtypes of PG-receptors.