Quantitative production of prostaglandin E2 and its metabolites by human fetal membranes

Cultured amnion, choriodecidua and intact fetal membrane produced similar quantities of prostaglandin E2 (PGE2) (1-5 ng/ml). Choriodecidua and intact fetal membrane also produced very high levels of PGE2 metabolites (100-1000 ng/ml). The total production of PGE (PGE2 + PGE2 metabolites) was similar in intact fetal membrane and in choriodecidua, suggesting that the amnion, although a source of PGE2, contributes little to the overall PGE production by fetal membranes.     

Maternal plasma prostaglandin E2 metabolite levels during human pregnancy and parturition

Summary. Because of methodological problems associated with the measurement in biological fluids of both prostaglandin E₂ (PGE₂) and its unstable principal circulating metabolite 13,14-dihydro-15-keto-PGE₂ (PGEM), there is little reliable information on these prostaglandins in human pregnancy and parturition. The recent discovery of a stable PGEM degradation product 11-deoxy-13,14-dihydro-15-keto-11β, 16-cyclo-PGE₂ (bicyclo-PGEM) has provided a means of studying endogenous plasma levels of PGEM which circumvents the problems encountered with direct measurements of PGE₂ and PGEM. Using a radioimmunoassay for bicyclo-PGEM we have therefore determined maternal peripheral plasma PGE₂ metabolite levels during human gestation. PGE₂ metabolite levels did not alter significantly during the second or third trimesters nor during labour. This contrasts with maternal peripheral plasma levels of the principal circulating metabolite of PGF_2α 13,14-dihydro-15-keto-PGF_2α (PGFM) which increases several fold during labour. Compared t o PGE₂ therefore. PGF_2α may be quantitatively the more significant prostaglandin associated with human parturition.     

Vitamin D3 metabolites stimulate prostaglandin production by human fetal membranes and placenta in vitro

In the present study we examined whether the vitamin D3 metabolites, 25-hydroxyvitamin D and 1-25-dihydroxycholecalciferol affected the production of the prostaglandins PGE2 and PGF2 alpha in human fetal membranes and placenta in vitro. Human amnion, chorion, decidual, and placental cells were maintained in primary monolayer culture. Treatment with the vitamin D3 metabolites resulted in an increase in PGE2 and PGF2 alpha production by amnion, decidua, and placental cells; however, these effects varied with time and were different between tissues. Although there was no significant increase in the production of PGE2 and PGF2 alpha by chorion cells in vitro, there was a significant increase in the production of prostaglandin F metabolites after treatment with the vitamin D3 metabolites. The data suggest that the vitamin D3 metabolites may increase free calcium availability and the conversion of arachidonic acid to the prostaglandins. The data do not, however, exclude the possibility that the vitamin D3 metabolites act at other points of arachidonic acid metabolism. These findings raise the possibility of a paracrine role for the vitamin D3 metabolites in the modulation of prostaglandin production within the human fetal membranes and placenta.     

Oral Prostaglandins E2 and F2a in the Induction of Labour

Summary: Oral prostaglandins E₂ and F_2a were used to augment amniotomy in the induction of labour in 173 patients. The success rate was significantly higher with prostaglandin E₂ than with prostaglandin F_2a (89% and 75%, respectively). This was achieved despite a significantly lower incidence of gastrointestinal side effects. No serious maternal or fetal complications occurred with either drug. It is concluded that oral prostaglandin E₂ is more efficient than oral prostaglandin F_2a in the induction of labour.     

Prostaglandin E2, Fetal Maturation and Ovine Parturition

Summary: The major source of PGE₂ in ovine pregnancy is the placenta, with secretion occurring bidirectionally into fetal and maternal circulations. The placental output of PGE₂ appears to increase when demand on placental function is increased, suggesting that the normally observed increase in its concentration towards term is driven by the growing demands of the fetus. The fetal pituitary is also involved in the control of PGE₂ synthesis. PGE₂ has potent stimulatory actions on the fetal pituitary to increase both the absolute concentration and the bioactive fraction of ACTH-containing peptides in the fetal circulation. It also directly stimulates glucocorticoid secretion from the fetal adrenal gland.
We propose that PGE₂ provides a tonic stimulation of the fetal HPA axis in late gestation, contributing to phenomena such as the apparent insensitivity of the pituitary to Cortisol feedback and the increasing sensitivity of the fetal adrenal. Because of its apparent responsiveness to placental workload, it may transduce stimuli from the placenta and transmit them to the fetal HPA axis, giving a possible biochemical basis to the empirically observed correlation between fetal metabolic demand and gestation length.     

The use of 16,16-dimethyl-transδ2 prostaglandin E1 methyl ester (gemeprost) vaginal pessaries for the termination of pregnancy in the early second trimester. A comparison with extra-amniotic prostaglandin E2

Summary. The use of gemeprost pessaries has been compared in an open randomized trial with the extra-amniotic infusion of prostaglandin E₂ (PGE₂) for the termination of pregnancy between 12 and 16 weeks gestation. The success rates were 77% and 79% for the pessary and infusion group respectively, and these rates were unaffected by parity. There was no significant difference in the cumulative abortion rate between the two groups, nor were there differences in the induction-abortion interval, nor in the time taken to the onset of pain or bleeding. However, women in the pessary group required significantly less analgesia than those in the infusion group. Side-effects, experienced both during treatment and during the 6 weeks after abortion, were similar in both groups. Gemeprost vaginal pessaries are an effective alternative to the extra-amniotic infusion of PGE, for the termination of pregnancy in the early second trimester.     

Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2α

Summary. Menstrual fluid was collected in a contraceptive diaphragm from 16 women with primary dysmenorrhoea and 12 matched control subjects without dysmenorrhoea. Prostaglandins F_2α (PGF_2α), E₂ (PGE₂) and 6-oxo-prostaglandin F_1α (6-oxo-PGF_lα) were extracted and measured using gas-chromatography: mass spectrometry (GC:MS). The concentrations of both PGF_2α and PGE₂ were higher on days 1 and 2 in the dysmenorrhoea group than in the control group and the concentration of PGF_2α was higher on day 1 than on day 2 in the dysmenorrhoea group. The concentrations of 6-oxo-PGF_1α (the stable metabolite of PGI₂) were low in both groups. These results confirm suggestions that PGF_2α is important in the aetiology of dysmenorrhoea and also indicate that PGE₂ may be involved.     

Controlled study comparing vaginal prostaglandin E2 pessaries with intravenous oxytocin for the stimulation of labour after spontaneous rupture of the membranes

Summary. In a prospective randomized study, 36 patients with spontaneous rupture of the membranes of ≥4 h duration were stimulated with 3 mg vaginal prostaglandin E₂ pessaries or intravenous oxytocin. Oxytocin stimulation was associated with shorter labours and a lower incidence of abnormal cervimetric progress. Of the patients given prostaglandin pessaries, 40% required a second dose after 4 h for slow progress; 45% of the primigravidae subsequently developed abnormal labour which was corrected by augmentation with oxytocin in all cases. One caesarean section was carried out for disproportion, and the remaining 35 patients were delivered vaginally. Prostaglandin pessaries were not associated with an increased incidence of hyperstimulation or sepsis. In conclusion, although PGE₂ pessaries are safe in spontaneous rupture of the membranes, intravenous oxytocin is more efficient in stimulating labour.