Initiation Of Human Parturition Research Articles

Initiation of human parturition: signaling from senescent fetal tissues via extracellular vesicle mediated paracrine mechanism.

A better understanding of the underlying mechanisms by which signals from the fetus initiate human parturition is required. Our recent findings support the core hypothesis that oxidative stress (OS) and cellular senescence of the fetal membranes (amnion and chorion) trigger human parturition. Fetal membrane cell senescence at term is a natural physiological response to OS that occurs as a result of increased metabolic demands by the maturing fetus. Fetal membrane senescence is affected by the activation of the p38 mitogen activated kinase-mediated pathway. Similarly, various risk factors of preterm labor and premature rupture of the membranes also cause OS-induced senescence. Data suggest that fetal cell senescence causes inflammatory senescence-associated secretory phenotype (SASP) release. Besides SASP, high mobility group box 1 and cell-free fetal telomere fragments translocate from the nucleus to the cytosol in senescent cells, where they represent damage-associated molecular pattern markers (DAMPs). In fetal membranes, both SASPs and DAMPs augment fetal cell senescence and an associated ‘sterile’ inflammatory reaction. In senescent cells, DAMPs are encapsulated in extracellular vesicles, specifically exosomes, which are 30–150 nm particles, and propagated to distant sites. Exosomes traffic from the fetus to the maternal side and cause labor-associated inflammatory changes in maternal uterine tissues. Thus, fetal membrane senescence and the inflammation generated from this process functions as a paracrine signaling system during parturition. A better understanding of the premature activation of these signals can provide insights into the mechanisms by which fetal signals initiate preterm parturition.

Cytokines in preterm parturition

We have proposed a model in which the initiation of human parturition in the presence of infection is mediated by the host response. Systemic infections such as pyelonephritis, or localized intrauterine maternal infections such as deciduitis and cervicitis, might trigger parturition via the monocyte/macrophage system in both maternal blood and human decidua. According to this model, labor is to be considered an event that occurs when the intrauterine or maternal environment is hostile to the well-being of the fetus, as was supported by recent studies. From this point of view, the initiation of preterm labor may have survival value.

PATHOGENESIS OF PRETERM LABOR AND PRETERM PREMATURE RUPTURE OF MEMBRANES ASSOCIATED WITH INTRAAMNIOTIC INFECTION

We have proposed a model in which the initiation of human parturition in the presence of infection is controlled by the host. Systemic maternal infections such as pyelonephritis or localized infections such as deciduitis can trigger parturition by the activation of the monocyte and macrophage system in peripheral blood and human decidua. Preterm labor and preterm PROM can, according to this, be considered events that occur when the intrauterine or maternal environment is hostile and threaten the survival of the fetal-maternal pair. From this point of view, the initiation of preterm labor may have survival value. Why does intrauterine infection result in preterm labor in some cases and PROM in others? It is possible that regulation of different components of the host response has an important role to play in determining clinical presentation. Thus, if preferential activation of the host response leads to the secretion of uterotonic agents (i.e., prostaglandins), preterm labor will result. On the other hand, if the activation of the host response results predominantly in the production of proteases (i.e., leukocyte elastase and MMPs), patients are more likely to experience PROM. Preterm labor and preterm PROM can be considered expressions of the same basic phenomenon: activation of the host-defense macrophage system. Although we have provided evidence that infection is an important factor in the pathogenesis of these conditions, preterm parturition should be considered as a syndrome with multiple causes.

Increase in prostaglandin bioavailability precedes the onset of human parturition

The traditional paradigm that prostaglandins (PGs) are of central importance in the initiation of labor has been challenged. A group of investigators has recently reported that the amniotic fluid concentrations of PGE 2 and PGF 2α increase only late in the course of labor implying that ‘the accumulation of prostaglandins in amniotic fluid is an after-effect of labor and not indicative of a role of these compounds in the initiation of human parturition’. The present study was conducted to determine whether amniotic fluid prostaglandin concentrations increase prior to the onset of human labor, the central question in this controversy. Three amniocenteses were performed in 17 women with intrahepatic cholestasis of pregnancy — the first two prior to the onset of labor and the third during early spontaneous labor. PGE 2 and PGF 2α were measured with sensitive and specific radioimmunoassays. Amniotic fluid concentrations of PGE 2 and PGF 2α increased prior to the onset of spontaneous labor. An additional increase in the concentrations of PGE 2 and PGF 2α was found in samples obtained in early labor. We conclude that an increase in prostaglandin bioavailability precedes the onset of spontaneous human parturition.

The role of fetal myoglobin in the initiation of human parturition.

The aim of the present investigation is to study the effect of amniotic fluid myoglobin on prostaglandin synthesis by the fetal membranes. The paper presents results of radioimmunologic studies of myoglobin levels in various biological fluids during pregnancy: amniotic fluid, maternal serum samples obtained from an antecubital vein and the cervix, and neonatal urine. Amniotic fluid myoglobin levels were found to be significantly higher at term. Our results suggest that amniotic fluid myoglobin is likely to be derived from the fetus and excreted into amniotic fluid through fetal urine. Incubation of the fetal membrane with amniotic fluid, neonatal urine, and commercially available myoglobin enhanced phospholipase A2 activity, as well as arachidonic acid and prostaglandin F2 alpha production was compared to incubation with normal saline. The addition of anti-myoglobin antibodies to incubation media was found to block these effects. The results of our study show that myoglobin activates prostaglandin synthesis by the fetal membranes and stimulates the onset of labor.

Human fetal membrane contribution to the prevention of parturition: uterotonin degradation.

This investigation was conducted to evaluate the potential capacity of the human fetal membranes-decidua parietalis, and in particular the chorion laeve, to degrade uterotonins that are produced in amnion, are present in amniotic fluid, or both. The four uterotonins that have been evaluated most frequently as myometrial contractants potentially involved in the initiation of human parturition are prostaglandins, oxytocin, endothelin-1, and platelet-activating factor. We assessed the levels of mRNA and the specific activities (SAs) of enkephalinase (the plasma membrane endopeptidase that degrades endothelins) and prostaglandin dehydrogenase (PGDH) in human fetal membranes, i.e. amnion and chorion leave, and in decidua parietalis. The SA of oxytocinase (which inactivates oxytocin) in these tissues also was determined. The SA of enkephalinase in chorion laeve from all anatomical sites (singleton and diamnionic-dichorionic twin placentae) in all pregnancies studied (mean +/- SEM, 95 +/- 7.9 ng/min.mg protein; n = 28) is similar to that in human fetal kidney (89.5 +/- 2.8; n = 6). Kidney tissue is believed to be one of the richest sources of enkephalinase. The SAs of enkephalinase in amnion (18.3 +/- 2.3 nmol/min.mg protein; n = 29) and in decidua parietalis (31.8 +/- 6.7; n = 20) also were high, but significantly less than that in chorion leave. The level of enkephalinase mRNA in chorion laeve in singleton pregnancies is high, as is the SA of enkephalinase (111.9 +/- 10.6 nmol/min.mg protein; n = 17). In paired chorion laeve tissues from five diamnionic-dichorionic twin placentae, the SAs of enkephalinase in reflected chorion laeve (74 +/- 12.8; P < 0.06 compared with singletons) and fused chorion laeve (64.8 +/- 6.5; P < 0.001 compared with singletons) were similar. The SA of PGDH in reflected chorion leave (46.3 +/- 6.9 nmol/min.mg protein; n = 19) was significantly greater than that in decidua (16 +/- 5.5; n = 15). There was a significant correlation between the levels of PGDH mRNA and PGDH enzyme SA. In fused chorion laeve of diamnionic-dichorionic twin placentae, the SA of PGDH (14.9 +/- 7.3; n = 4) was much less than that in reflected chorion laeve of the same twin pregnancy (70.5 +/- 14.7; n = 4). PGDH mRNA was not detectable in amnion tissue (n = 5) by northern analysis, and the SA of PGDH (< 1.2 +/- 1.0; n = 6) in amnion was undetectable or near the lower limit of assay detection.(ABSTRACT TRUNCATED AT 400 WORDS)

The accumulation of prostaglandins (PG) in amniotic fluid is an aftereffect of labor and not indicative of a role for PGE2 or PGF2 alpha in the initiation of human parturition.

The accumulation of prostaglandins (PGs) in amniotic fluid (AF) during labor is cited frequently as one line of evidence in support of a role for these eicosanoids in the initiation of human parturition. In this study, we evaluated an alternate possibility, viz. that PGs entering AF at parturition are produced as a sequela of labor-associated processes. During labor, the AF normally becomes separated into two compartments, viz. the forebag and the upper compartment, by the obstruction produced as the descending fetal presenting part is engaged in the maternal pelvis. We theorized that the PGs that enter AF are produced in traumatized tissues lining the forebag, which is formed as the result of labor-driven cervical dilatation. In addition, these traumatized tissues are exposed to and bathed by the vaginal fluid, which contains many potent stimuli of PG formation, viz. large numbers of microorganisms and bacterial toxins. AF was collected at term before labor (n = 50) and from the upper compartment during labor (n = 47) by transuterine amniocentesis, and AF was collected by direct needle aspiration of the forebag during labor (n = 143). PGF2 alpha, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), and PGE2 were quantified by RIA. The concentrations (nanomoles per L mean +/- SEM) of PGs in AF of the forebag (PGF2 alpha, 85.6 +/- 10.6; PGFM, 20.8 +/- 2.58; PGE2, 26.9 +/- 2.73) were much greater than those in the AF before labor (PGF2 alpha, 0.56 +/- 0.05; PGFM, 0.9 +/- 0.08; PGE2, 5.89 +/- 1.13) or in AF of the upper compartment during labor (PGF2 alpha, 7.14 +/- 1.64; PGFM, 5.11 +/- 0.82; PGE2, 8.74 +/- 1.71). The concentrations of PGs in AF of the upper compartment during early labor (< or = 2.5-cm cervical dilatation) were no greater than those in AF before labor began. The concentration and total content of PGs in AF of the forebag increased as a function of cervical dilatation until delivery. At 3- to 5-cm cervical dilatation, the levels of PGs in AF of the upper compartment were greater than those before labor, but significantly less than those in AF of the forebag at the same stage of labor progress. After 3-5 cm, the levels of PGs in the upper compartment did not increase further. These findings indicate that PGF2 alpha, PGFM, and PGE2, which enter AF in increased amounts during parturition, are produced during, not before, labor in tissues (principally decidua) lining for forebag.(ABSTRACT TRUNCATED AT 250 WORDS)

The accumulation of prostaglandins (PG) in amniotic fluid is an aftereffect of labor and not indicative of a role for PGE2 or PGF2 alpha in the initiation of human parturition

The accumulation of prostaglandins (PG) in amniotic fluid is an aftereffect of labor and not indicative of a role for PGE2 or PGF2 alpha in the initiation of human parturition

Exposure of human amnion to amniotic fluid obtained before labor causes a decrease in chorion/decidual prostaglandin release.

Prostaglandin (PG) production by fetal membranes has been implicated in the initiation of human parturition, but its regulation is not well understood. We used an in vitro system to study paracrine control of term, fetal membrane PG production. Using a modified Ussing chamber, full thickness fetal membranes with attached decidua were sealed into a chamber so that each hemichamber was a compartment for either the fetal (amnion) or maternal (chorion/decidua) side. Released PGs from maternal and fetal sides were then measured after exposure of the amnion to either buffer or amniotic fluid. We found that basal release of PGs from both the fetal and maternal sides was 2- to 3-fold higher in membranes obtained after labor compared to those obtained before labor. When amnion obtained after labor was exposed to amniotic fluid, we found a 3- to 5-fold increase in the net release of PGE2 from the amnion; however, the maternal side showed an unexpected relative decrease in PGE2 and PGF2 alpha release. This was a paracrine effect, since direct exposure of chorion/decidua to amniotic fluid caused increased release of the PG precursor, arachidonic acid. Direct transfer of radiolabeled PG from fetal to maternal side was minimal.

Identification by flow cytometry of the prostaglandin-producing cell populations of term human decidua

Human term decidua produces prostaglandins (PGs) which have been implicated in the initiation of human parturition. Using flow cytometry to isolate pure cell populations, we have investigated the cell types responsible for decidual PG production. Cell dispersions were prepared enzymatically from decidua vera isolated from term placentae, and were incubated in Dulbecco's Modified Eagle's Medium containing 0.25% bovine serum albumin at 37 degrees C. PGF2 alpha and PGE2 output were measured by radioimmunoassay of the conditioned medium. Production of PGF2 alpha (fmol/10(6) cells per 3 h) exceeded that of PGE2 at 273 (108-322) versus 97 (38-127) respectively (median (range]. The decidual cell dispersions were then incubated with monoclonal antibodies (anti-CD45 which labels the leukocyte common antigen or anti-human leukocyte antigen class II (HLA-DR) which is specific for macrophages in this tissue) and sorted by flow cytometry. The resultant antibody-positive and -negative cell populations were incubated and PG production was measured. Controls showed that antibody labelling and sorting did not alter PG production. PGF2 alpha and PGE2 output by bone marrow-derived (CD45-positive) cell populations exceeded that of non-bone marrow-derived (CD45-negative) cells. Furthermore, we were able to demonstrate that the HLA-DR-positive macrophage population had the highest PGF2 alpha and PGE2 production rates in human term decidua in vitro.

Cytokines and infection-induced preterm labour

Our present understanding of the physiologic role of prostaglandins during pregnancy and, in particular, the precise function of these agents in the initiation of human parturition, is limited. This uncertain posture persists in spite of evidence (reviewed in detail recently by Challis and Olson 1988) in favour of a fundamental role for prostaglandins in a host of physiological processes in reproductive biology, including the onset and progression of labour. All investigators agree that prostaglandin E2 (PGE2) and prostaglandin F2, (PGF2,) can act, pharmacologically, as uterotonins (to cause myometrial contraction) when administered to pregnant women at any stage of gestation; moreover, the ingestion of inhibitors of prostaglandin synthesis by pregnant women is associated with a delay in the onset of labour-whether spontaneous or induced. There is much evidence in support of the conclusion that there is an increase in the rate of production of prostaglandins during labour: namely, during labour, there are increases in the levels of PGE2, PGF2, and 13,14-dihydro-15-keto-PGF2, (PGFM) in amniotic fluid and increases in PGFM in maternal blood. Also, prostaglandins will effect cervical dilatation. However, it has not been proven that prostaglandins serve as the physiological uterotonins of parturition or that prostaglandins are obligatorily involved in parturition at all stages of pregnancy, i.e. term and preterm labour. The evidence that there is an increase in the levels of prostaglandins in the maternal or fetal compartment prior to the onset of labour is limited. The possibility that the increase in prostaglandins is a consequence of labour (and not an initiating event) has not been excluded. Importantly, based on the findings of studies conducted recently, the possibility exists that labour (and delivery) may occur in some preterm pregnancies in the absence of an increase in prostaglandin production of the same magnitude that occurs during normal labour at term (Cox et al. 1989). Thus, we suggest that it is timely to consider the role of prostaglandins in the parturitional process with a new view, i.e, one that may enable an expansion of our understanding of the biochemical events involved in the initiation of parturition at term and preterm. Nowadays, the statement that human pregnancy is characterized by profound alterations in a host of biochemical and physiologic processes that encompass most all organ systems may rightly be considered timeworn. Yet, recent analyses of this well-recognized premise have led to the concepts that among these pregnancy-altered processes are those that facilitate recognition of pregnancy and, thereby, adaptation to pregnancy and maintenance of pregnancy. Perhaps the most remarkable compliance of normal human pregnancy is the maintenance of uterine quiescence for 38 weeks. For more than 99% of gestation, normal pregnancy is characterized by remarkable uterine repose and equanimity -a state that is essential to the maintenance of pregnancy. This quiescent state is uncommon for this smooth

Changes in prostaglandin transfer across human fetal membranes obtained after spontaneous labor

Increased prostaglandin E2 production from amnion is thought to be a critical step in the initiation of human parturition. However, it is not known whether amniotic prostaglandin E2 can reach the decidua and/or myometrium. We examined whether prostaglandin E2 could cross the amnion and full-thickness membranes and whether this capacity changed with active labor. Using an in vitro system we found that there was a time-dependent cumulative transfer of total radioactivity and of radioactivity corresponding chromatographically to prostaglandin E3 across amnion and full-thickness membranes. The rate of transfer across the amnion was faster than across full-thickness membranes and varied according to the site of tissue sampling within the uterus. The permeability constant for prostaglandin E2 transfer across full-thickness membranes was significantly higher in tissue collected after the spontaneous onset of labor than in tissue collected at elective cesarean section at term. We conclude that prostaglandin E2 produced in human amnion at term may escape metabolism in the chorion and reach the decidua and/or myometrium.

Metabolism of platelet-activating factor (1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine) in human fetal membranes and decidua vera

We have previously reported that platelet-activating factor (PAF) is present in human amniotic fluid obtained from women in labor. We have also demonstrated that PAF, lyso-PAF, and alkyl acyl- sn-glycero-3-phosphocholine (AA-GPC) are present in human amnion tissue. In the reported study, we have investigated the enzymes involved in PAF metabolism in amnion tissue and their regulation. A phospholipase A 2 activity has been demonstrated in amnion tissue which cleaves alkyl acyl (long-chain) sn-glycero-3-phosphocholine. The enzyme activity is not altered by Ca 2+ and is distinctly different from the phospholipase A 2 that we have previously characterized in this tissue. Amnion tissue contains acetyltransferase activity which requires Ca 2+ and is associated with the microsomal fraction. Acetylhydrolase is also present in the cytosolic fraction of amnion tissue. Acetylhydrolase activity has also been demonstrated in amniotic fluid. The affinities of acetyltransferase (for lyso-PAF) and acetylhydrolase (for PAF) were unaffected by Ca 2+. In the presence of Ca 2+, however, the specific activity of acetyltransferase was increased four- to fivefold while that of acetylhydrolase was unaffected. Acetyltransferase and acetylhydrolase activities in fetal membranes and decidua were similar and were unchanged with gestational age. The possible role of PAF in the initiation of human parturition is discussed.

Prostaglandins, not cyclic GMP, inhibit oxytocinase isoenzymes from human amniotic fluid in vitro

Two isoenzymes of oxytocinase (EC 3.4.11.3) activity were fractionated from human amniotic fluid samples between the 14th and 22nd weeks of gestation by Ultrogel acrylamide-agarose gel filtration and partially characterized. The isoenzymes were competitively inhibited by PGE 1, PGE 2 and PGF 2 α more at pH 6.2 than at pH 6.8, whereas cyclic GMP (cGMP) and its 8-bromo derivative had no effect at either pH. The implications of these findings are discussed and it is suggested that since the activity of amniotic fluid oxytocinases is very low or minimal at or near term, inhibition of these by prostaglandins may not have physiological significance in the initiation of human parturition.

Another look at initiation of human parturition.

Despite our moderate understanding of the physiology of the initiation of labour in various animal species, notably ruminants and rodents, the mechanism in man remains enigmatic. In the initiation process in the human the major role is apparently taken by the placental and fetal membranes, while the fetus may modulate the timing of labour. This review sets out to examine current knowledge of the process of initiating and maintaining parturition in the human.

Progesterone, cortisol and oestradiol-17 beta in the initiation of human parturition: partitioning between free and bound hormone in plasma.

The concentrations of total and free progesterone, oestradiol-17 beta, and cortisol were measured in the plasma of 24 pregnant women from 10-17 days prepartum, during labour, and for 2-3 days postpartum. All the women were delivered vaginally, and their hormonal profiles were similar, whether they initiated labour spontaneously (n = 11) or were induced by rupture of the fetal membranes (n = 13). Before labour, the plasma concentrations of total radioimmunoassayable progesterone, oestradiol-17 beta and cortisol were 557.3 (SEM 70.3) nmol/l and 590.0 (SEM 76.7) nmol/l, 94.3 (SEM 18.7) nmol/l and 111.6 (SEM 19.8) nmol/l, and 1087.2 (SEM 103.7) nmol/l and 1020.7 (SEM 100.7) nmol/l, for the spontaneous and induced groups, respectively. During labour progesterone and oestradiol-17 beta declined in maternal plasma to around 130 nmol/l and 30 nmol/l in both groups by the end of the third stage. The free fractions of progesterone and oestradiol-17 beta remained constant throughout labour and over the entire study period at 2-3% and 1-2%, respectively. Total plasma cortisol rose to 1243.7 (SEM 83.3) nmol/l (P less than 0.02, spontaneous group) and 1247.5 (SEM 97.4) nmol/l (P less than 0.001, induced group) by the end of the first stage of labour. Concomitantly, free cortisol increased from 4.5-5.5% to 7.2-8.2% over this period so that its concentration increased by approximately 2.5-fold in both groups of women during labour. We conclude that the total and physiologically-active free concentrations of progesterone and oestradiol-17 beta in maternal plasma do not change immediately before the onset of labour.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxytocin and the initiation of human parturition: III. Plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2α in spontaneous and oxytocin-induced labor at term

The plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2α (PGFM) were measured in serial samples collected during the first stage of spontaneous and oxytocin-induced labor in 17 and 15 women, respectively. Four women in late pregnancy served as control subjects, with serial samples collected at similar intervals as during labor. During spontaneous labor, mean plasma oxytocin levels were consistently raised over the levels observed 1 to 2 weeks before the onset of labor and were higher than the levels in the control patients (mean, 19.9 ± 3.1 pg/ml) and the initial levels in the oxytocin-induced group of women (mean, 17.4 ± 4.8 pg/ml). The mean plasma oxytocin levels during spontaneous labor (45 ± 3.9 pg/ml) were similar to those observed during infusion of 4 to 6 mU/min of synthetic oxytocin (49.1 ± 10.9 pg/ml). Plasma oxytocin levels increased progressively with stepwise increments of the infusion. Plasma PGFM levels also rose during labor, but, in contrast to the oxytocin levels which increased in early labor, plasma PGFM levels did not increase significantly until relatively late in labor, provided the membranes were intact. The state of the membranes had a marked influence on plasma PGFM; patients with spontaneous rupture of membranes had significantly increased PGFM levels when admitted early in labor or when membranes ruptured during labor. This increase in prostaglandin F2α (PGF2α) production does not by itself suffice to initiate labor, as evidenced by the failure of premature rupture of the membranes to initiate labor in a number of patients with elevated PGFM levels in whom labor was then induced with oxytocin. Conversely, oxytocin induction was successful only when PGFM levels increased during the infusion of oxytocin; in the absence of a rise in plasma PGFM, oxytocin induction failed. These data add support to the view that both oxytocin and PGF2α are required for adequate stimulation of the human uterus during labor. In addition, the data suggest that oxytocin rather than PGF2α may be the major stimulus that initiates labor, whereas PGF2α appears responsible for the progress of labor.

Oxytocin and the initiation of human parturition: IV. Plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2α during induction of labor by artificial rupture of the membranes

The influence of artificial rupture of the membranes on plasma levels of 13,14-dihydro-15-keto-prostaglandin F2α (PGFM) and oxytocin was examined in 23 pregnant women at term. Serial blood samples were collected before and 15 minutes, 2 hours, 5 hours, and 8 hours after artificial rupture of the membranes. A significant rise in the concentration of plasma PGFM was observed at 15 minutes in the majority of women (20 of 23), but the magnitude of this early rise or the lack thereof was not related to the subsequent course of labor. The concentration of plasma PGFM at 2 hours was, on the other hand, significantly correlated with the induction-delivery interval. Amniotomy, by itself, induced labor and delivery when the increased PGFM levels were maintained from 2 to 5 hours after the procedure (n = 16). In those cases where Pitocin stimulation was required for adequate uterine contractions, it was found that plasma PGFM levels had declined to initial values at 2 hours. Pitocin infusions then partially reversed this decline. In one patient, the cervix failed to dilate in spite of prolonged Pitocin infusion which did not induce significant uterine contractions, and the infusion did not reverse the marked fall in plasma PGFM after the early but transient rise. Mean plasma oxytocin levels did not rise significantly during labor induced by artificial rupture of the membranes and were, on the average, similar to the levels observed during the first stage of spontaneous or oxytocin-induced labor. Considering the previously demonstrated maximal levels of uterine oxytocin receptors in early labor, the absence of a rise in the plasma oxytocin levels does not negate a role for oxytocin in working synergistically with prostaglandins in the mechanism of labor.

Initiation of labor: Husslein P, Fuchs A, Fuchs F. Oxytocin and the initiation of human parturition 1. Prostaglandin release during induction of labor by oxytocin. Am J Obstet Gynecol 141:688 (1981). 11. Stimulation of prostaglandin production in human decidua by oxytocin. Am J Obstet Gynecol 141:694 (1981)

Initiation of labor: Husslein P, Fuchs A, Fuchs F. Oxytocin and the initiation of human parturition 1. Prostaglandin release during induction of labor by oxytocin. Am J Obstet Gynecol 141:688 (1981). 11. Stimulation of prostaglandin production in human decidua by oxytocin. Am J Obstet Gynecol 141:694 (1981)

Initiation of human parturition: XIV. Increase in the diacylglycerol content of amnion during parturition

Arachidonic acid (the precursor of prostaglandins of the 2-series and related compounds) is released from phosphatidylinositol in a reaction sequence catalyzed by three enzymes, i.e., phospholipase C, diacylglycerol lipase, and monoacylglycerol lipase. Diacylglycerol, an intermediate in this pathway, was found in human amnion tissue. The fatty acid composition of the diacylglycerol fraction of amnion tissue was very similar to that of the phosphatidylinositol fraction. The diacylglycerol content of human amnion tissue obtained during early labor was greater than that of amnion tissue obtained before the onset of labor. These findings are supportive of the proposition that arachidonic acid is released from the phosphatidylinositol of amnion tissue during human parturition.