Uterine activity and prostaglandin production following intraamniotic hyperosmolar urea

The relationship between endogenous prostaglandin (PG) production and uterine activity was studied in hyperosmolar urea induced abortion patients. Polygraphic recordings of intraamniotic pressure were obtained at periodic intervals following intraamniotic injection of 80 gm urea. At 0, 0.25, 1, 4 and 8 hours amniotic fluid and blood samples were obtained for PGE, PGF and 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) analysis by radioimmunoassay. Blood was also sampled at time of absorption. In eight patients studies, uterine tone was elevated by 0.25 hour although no rhythmic contractions were observed by 1 hour. At 4 hours, amniotic fluid PGF concentration increased significantly (P < .01) over the pre-injection value and continued to increase at 8 hours. Amniotic fluid PGE, PGFM and all plasma PG's showed no change during the 8 hour period following urea administration. At time of abortion the plasma PGFM concentration was significantly greater than at the time of injection (238 ± 54.4 vs. 86.7 ± 7.3 pg/ml). There was no significant differences between pre-injection and absorption plasma PGF or PGE concentrations. In the present study, there is no evidence that increased prostaglandin production precedes urea induced contractions. The possible role of PG's in uterine contractions is discussed.     

Prostaglandins in fetal tracheal and amniotic fluid from late pregnant sheep

Concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in fetal tracheal and amniotic fluid from chronically catheterized sheep during late pregnancy. Amniotic fluid contained significantly greater concentrations of these prostaglandins than tracheal fluid (p less than 0.01); there was no correlation between the level of prostaglandins found in each fluid. In tracheal fluid concentrations of PGE and PGFM exceeded those of PGF (P less than 0.01) whereas no significant differences were found in amniotic fluid. The levels of prostaglandins in these fluids were similar in ewes bearing hypophysectomized fetuses.     

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometriu. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.     

Production of prostaglandin by late-gestation porcine placental cells in vitro.

Fifteen sows were assigned to three groups of five each, according to gestational age (109 days, 114 days or labour). Two fetuses per sow were chosen at random, and amnion, allantochorion, amniochorion, amniotic fluid and fetal urine were collected. Tissues were enzymatically dispersed and incubated for 1, 2, 3 or 4 h and the prostaglandin (PG) content of the supernatant medium was measured by radioimmunoassay. In general, all placental cell types produced at least three times more prostaglandin E (PGE) and 6-keto-PGF1 alpha than PGF. Production did not vary across gestational age, except that production of 6-keto-PGF1 alpha was lower in cells collected during labour, resulting in a relative increase in PGF and PGE. Aminochorion cells had a lower de novo capacity to synthesize PG than did allantochorion or amniochorion, whereas treatment of allantochorion with preterm amniotic fluid, preterm or term fetal urine resulted in increased PG output. These results demonstrate that porcine placental cells can synthesize and metabolize prostaglandin in late gestation but suggest that their capacity to produce PGI2 (as measured by 6-keto-PGF1 alpha) is lower than for other prostaglandins during labour.     

Radioimmunoassay measurement of ACTH-facilitated PGE2 and PGF2α release from isolated cat adrenocortical cells

Prostaglandin (PG) biosynthesis by trypsin-dispersed cat adrenocortical cells was studied by radioimmunoassay (RIA). Parallel assays of incubation media using PGF_2α and PGF_1α antisera established that PGF_2α is the primary PGF released by feline cortical cells. Following the reduction of PGE to PGF with sodium borohydride (NaBH₄) these same two antisera were also used to identify PGE₂ as the primary PGE released. RIA using a PGE antiserum confirmed the presence of PGE in the incubation medium. Steroidogenic concentrations of ACTH (50–250μU) enhanced PGE and PGF release, and indomethacin suppressed the ACTH-facilitated release. These studies provide additional evidence for ACTH-induced PG synthesis by feline cortical cells, and support the hypothesis that PGs play some role in the steroidogenic action of ACTH.     

Uterine prostaglandin concentrations following fetal death in sheep

Concentrations of prostaglandin E (PGE), PGF and 6-oxo-PGF_1α (the hydrolytic product of PGI₂) were measured by radioimmunoassay (RIA) in myometrium, endometrium, cotyledons, amnion and chorioallantois taken from different uterine areas from chronically catheterized sheep bearing fetuses which had died 12–26 h previously (n=4) or 34–72 h previously (n=4). These two groups of animals were designated fetuses dead <30 h and >30 h respectively. The time of fetal death was assessed on the basis of fetal heart rate and blood gases. At the time of the tissue collection the ewes were between 123 and 130 days after mating. For comparative purposes, tissues also were collected from four sheep bearing live chronically catheterized fetuses at 130 days of gestation.For myometrium, concentration of PGF, PGE and 6-oxo-PGF_1α were significantly higher in sheep bearing dead fetuses, compared to those bearing live fetuses. Analysis of variance also showed a significant effect of uterine area on myometrial PGE concentrations, concentrations being higher in tubal areas than elsewhere. Concentrations of PGE, PGF and 6-oxo-PGF_1α were higher in endometrium taken from uteri containing dead fetuses. In cotyledons, concentrations of PGF and 6-oxo-PGF_1α but not PGE, were significant elevated following fetal death. Concentrations of 6-oxo-PGF_1α, but not PGE or PGF, were elevated in both chorioallantois and amnion of sheep bearing dead fetuses, compared to those bearing live fetuses. In association with elevated PG concentrations, there was a progressive increase in the frequency and maximum amplitude of uterine contractions. These results show that PG concetrations are elevated following fetal death in sheep, and suggest an association between elevated PG concentrations and delivery of the dead fetus.     

Effects of beta-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep

Recent studies have reported that beta-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether beta-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the beta-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 microgram.kg-1.min-1; (b) Isop at a dose of 0.08 microgram.kg-1.min-1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 microgram.kg-1.min-1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2 alpha or 13,14-dihydro-15-keto-PGF2 alpha (PGFM] concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 microgram.kg-1.min-1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2 alpha or PGFM) concentrations. No changes in plasma PGE2, PGF2 alpha, or PGFM occurred during saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of gestational age and onset of labour on determinants of fetal-maternal fluid and electrolyte balance in sheep.

Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se.     

Prostaglandins in maternal and fetal plasma and in allantoic fluid during the second half of gestation in the mare.

The concentrations of the primary prostaglandins (PG) F-2alpha and E-2 and the metabolite 13,14-dihydro-15-oxo-prostaglandin (PGFM) in maternal and fetal plasma and in allantoic fluid were measured in chronically catheterized mares and fetuses. A gradual rise in all 3 PGs occurred with increasing gestational age. PGE-2 and PGF-2 alpha levels were highest in the allantoic fluid and lowest in the maternal plasma, whereas PGFM concentrations were greatest in maternal plasma. Significant venous-arterial plasma differences in PGFM concentration were detected across the uterine circulation between 180 and 280 days gestation. The 3--5-fold rise in maternal PGFM associated with fasting or intrauterine surgery was virtually abolished by meclofenamic acid, a prostaglandin synthetase inhibitor. Increases in PGE-2 and PGF-2 alpha in the fetal fluids preceded premature delivery of the foal, while PG changes in maternal plasma were minimal even 10--20 h before delivery.     

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition

A method of tissue superfusion has been used to measure $\text{in vitro}$ prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105–135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F_1α were generally low. Thromboxane B₂ (TXB₂) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF_1α by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 ± 4.1 to 43.8 ± 7.4 ng/g. dry wt./min; 6-oxo-PGF_1α production rates increased more than three-fold from 10.0 ± 2.7 to 34.6 ± 9.8 ng/g. dry wt./min (means ± S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB₂ by the two groups.     

The modulation of prostaglandin synthesis by peritoneal fluids

Biological fluids from several sources (e.g. blood, fetal urine, amniotic fluid) have been shown to contain factors that modulate prostaglandin (PG) synthesis. In this study, we investigated the possibility that peritoneal fluid contains substances that may regulate PG synthesis. Peritoneal fluids were obtained from women undergoing diagnostic laparoscopy for infertility. Fluids from women without evident pelvic pathology were incubated with prostaglandin synthase prepared from bull seminal vesicles in the presence of excess arachidonic acid, and the production of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha was quantified by specific radioimmunoassay. The untreated fluids inhibited potently the synthesis of PGE2 but such inhibitory activity was not extractable by chloroform:methanol. An ultrafiltrate of the fluid containing molecules smaller than 10,000 Daltons stimulated PGF2 alpha synthesis but this activity was also lost after extraction. The extracted fluid did, however, stimulate the synthesis of prostacyclin (as reflected by 6-keto-PGF1 alpha).     

Paraplacental passage of 3H-prostaglandin F2

Prostaglandins F_2α permeates the live and denaturated whole fetal membranes as well as their isolated components chorion and amnion. The permeability constant in our vitro method is 1.3 × 10^?3 cm/min for PG. If 40 mg PG are instilled intra-amniotically at term — as used in therapeutical abortion — then 3.7 mg prostaglandin F_2α would pass per hour from the amniotic fluid through the fetal membranes into the decidua.     

Production of prostaglandins by fetal rat lung type II pneumonocytes and fibroblasts

The output of prostaglandins I2, E2, F2 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) from third passage day 20 rat fetal fibroblasts and type II alveolar pneumonocytes was studied. In 2 h incubations, the output levels for each cell type were: PGI2 greater than PGE2 much greater than PGF2 alpha = PGFM when cells were incubated with Ca2+ ionophore A23187 (10 microM) or arachidonic acid (1 microgram/ml).     

Selective elevation of circulating prostaglandin concentrations in hyaline membrane disease in pre-term infants

The plasma concentrations of prostaglandins E and F (PGE, PGF) and 13,14-dihydro-15-keto-PGF (PGFM) have been measured in pre-term neonates with hyaline membrane disease (HMD) and controls. The concentrations of PGF and PGFM were significantly higher in infants having HMD with a disproportionate increase in PGFM levels for the increase in PGF found. The vasoconstrictor nature of PGF may contribute to the morbidity associated with HMD and the possible therapeutic benefit from the use of prostaglandin synthetase inhibitors is discussed.     

The effect of indomethacin on ovarian prostaglandin release in hens

Indomethacin, an inhibitor of prostaglandin (PG) synthetase, will block uterine muscle electromyographic activity (EMG activity) and oviposition at a midsequence oviposition and ovulation in domestic hens, but does not block the increase in EMG activity associated with the first ovulation of a sequence. To assess the potential relationship between prostaglandin release from the ovarian follicles and EMG activity in egg-laying hens, we determined the concentrations of PGF2 alpha, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), and PGE2 in brachial, ovarian follicular and uterine venous plasma and tissues in relation to uterine muscle EMG activity at the first ovulation and at a midsequence oviposition. The concentrations were measured after an i.m. injection (25 mg/hen) of indomethacin. In control hens sampled hourly, beginning 4 h before the peak of EMG activity at the first ovulation of a sequence, there was a sharp increase (p less than 0.05) in concentrations of PGF2 alpha and PGFM in brachial vein plasma coincident with the increase (p less than 0.05) in uterine EMG activity. Hens pretreated with indomethacin also had increased plasma PGF2 alpha and PGFM levels (p less than 0.05) in brachial vein plasma and increased uterine EMG activity (p less than 0.05) at this time. Indomethacin treatment lowered but did not eliminate mean levels of PGF2 alpha in the venous effluent from the largest preovulatory follicle at the first ovulation (36.0 +/- 9.9 ng/ml vs. 14.4 +/- 1.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Amniotic fluid concentrations of prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11, 16-cyclo-prostaglandin E2 (PGEM-LL) in preterm labor

Although prostaglandins (PGs) are considered the key mediators of human parturition at term, there is a paucity of data regarding their participation in the mechanisms responsible for preterm labor. The purpose of this study was to establish if preterm labor is associated with changes in the amniotic fluid concentrations of prostaglandins. PGF2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-prostaglandin E2 (PGEM-ll) were measured by using specific and sensitive radioimmunoassays. Amniotic fluid was retrieved by transabdominal amniocentesis from 55 women with preterm labor and intact membranes. Patients were divided into three groups according to the response to tocolysis and the presence or absence of an intra-amniotic infection. Amniotic fluid concentrations of PGFM and PGEM-ll were significantly greater in women with preterm labor and intra-amniotic infection than in women without infection. In addition, patients unresponsive to tocolysis without intra-amniotic infection also had a significantly greater concentration of PGFM and PGEM-ll in amniotic fluid than those responsive to tocolysis. Amniotic fluid concentrations of PGF2 alpha were greater in women with intra-amniotic infection than in women without intra-amniotic infection. In the absence of intra-amniotic infection, no difference in amniotic fluid PGF2 alpha concentrations could be found between women who responded to tocolytic treatment and those who did not.     

Prostaglandin release from preparations used vaginally for the induction of labour

The release and absorption profiles from the vagina of PGE2 in different vehicles used for cervical ripening and labour induction have been studied observing changes in concentrations of PGE metabolite (PGEM) and PGF metabolite (PGFM). In all groups a rise in PGEM concentration occurred over the 6 hour observation time but with wide variation. The profiles obtained differed markedly between the preparations under investigation correlating with the uterine contractions generated. PGFM generally showed little change. The model used could be explored further to enable modification of the vehicles used for PGE2 incorporation to achieve improved clinical results.     

F prostaglandin levels in amniotic fluid in premature labour

The concentration of prostaglandin F (PGF) in amniotic fluid was measured by radioimmunoassay in 27 patients admitted in premature labour. There was a strong correlation between PGF levels in amniotic fluid and both cervical dilatation (r = 0.81; P < 0.001) and duration of labour (r = 0.79; P < 0.001). Cervical dilatation greater than 7 cm was associated with levels exceeding 2000 pg/ml. When contractions were present for less than one hour, levels of PGF were below 50 pg/ml. Low levels of PGF were found in amniotic fluid from a separate group of three patients, of whom two had cervical incompetence. It is concluded that the onset of premature labour is not associated with elevated levels of PGF in amniotic fluid. During premature labour, concentrations rise to an extent comparable to that observed in labour at term.     

A dystocia and caesarean section model to characterize uteroplacental prostaglandin concentrations associated with retained placenta in dairy cattle

Plasma concentrations of prostaglandin F(2a) (PGF(2a), 13, 14-dihydro-15-keto-prostaglandin F(2a) (PGFM), prostaglandin E(2) (PGE(2)) and 13,14-dihydro-15-keto-prostaglandin E(2) (PGEM) were determined by RIA in blood samples taken from the jugular vein and the uteroplacental circulation (umbilical vein, umbilical artery and uterine vein) of 13 Holstein Friesian cows during caesarean section. According to discharge of placenta cows were divided in 2 groups. Group I (shedding of placenta within 12 hours, NRP, n=8) and Group II (retained placenta, RP, n=5). In blood samples taken from the jugular vein before surgery, no significant differences existed between groups regarding PGF(2a), PGFM, PGE(2) and PGEM. Concentrations of PGF(2a) and PGFM in the uteroplacental circulation of NRP cows were significantly higher than those of RP cows (except for PGFM in the umbilical vein). For all sampling sites except the jugular vein before surgery, PGE(2) and PGEM levels of NRP cows were significantly higher compared to RP cows.     

Influence of cortisol on prostaglandin synthesis by fetal membranes, placenta, and uterus of pregnant rabbits

Two experiments were designed to assess the effects of cortisol on prostaglandin formation in amniotic fluid and the prostaglandin-forming cyclooxygenase in 4 gestational tissues of rabbits. Cortisol treatment (12 mg/kg body wt/h) was initiated on Day 21 of pregnancy and continued for a 24-h period. Each experiment included 5 treated and 5 vehicle-injected controls, killed at 48 (Experiment 1) or 62 h (Experiment 2) after initial injection. In both experiments, amniotic fluid was collected; cortisol, prostaglandin F (PGF), and prostaglandin E2 (PGE2) were quantified by radioimmunoassay. Microsomes prepared from amnion, yolk sac splanchnopleure, uterus, and placenta were analyzed for prostaglandin-forming cyclooxygenase activity. In Experiment 2, blood drawn at 12-h intervals was quantified for PGF, PGE2, and progesterone. In cortisol-treated rabbits, plasma progesterone decreased (p less than 0.01) from 7.2 +/- 0.8 ng/ml on Day 21 (pre-treatment) to 1.6 +/- 0.2 ng/ml on Day 23, 48 h after the initiation of cortisol treatment. By 62 h, PGF, PGE2, and cortisol concentrations were all significantly higher (p less than 0.05) in the amniotic fluid of treated animals. However, prostaglandin-forming cyclooxygenase activity had not increased in most fetal or maternal tissues at either 48 or 62 h. Therefore, even though increased prostaglandin production may be responsible for the cortisol-induced abortion, increased cyclooxygenase activity in the fetal membranes, placenta, or uterus probably is not the primary stimulus for the increased prostaglandin synthesis.