Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy.
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Human labour is associated with increased prostaglandin synthesis within the fetal membranes. We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels. COX-1 mRNA expression was low in human amnion and chorion-decidua and did not change with gestational age. COX-2 mRNA expression in fetal membranes increased with gestational age, with significant up-regulation prior to the onset of labour and in association with labour. Protein concentrations of COX-1 did not change, whilst concentrations of COX-2 increased from the first to the third trimester. COX activity increased with gestational age and in association with labour, although prostaglandin production in fetal membranes collected after labour was reduced, suggesting reduced substrate supply. These data suggest that it is up-regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin synthesis within the fetal membranes at term. Much of the increase in COX-2 expression precedes the onset of labour, suggesting that it is a cause, rather than a consequence, of labour. (+info)
Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour.
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Oxytocin receptor (OTR) mRNA expression has previously been demonstrated in human myometrium, decidua, chorion and amnion but the effect of gestational age and the onset of labour has not been determined in these individual tissues. Spatial OTR mRNA expression was examined by in situ hybridization and ligand binding was confirmed using autoradiography with the iodinated oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin (125I-OTA). Tissue was collected at term (>37 weeks of gestation) or preterm (24-36 weeks of gestation) caesarean section and classified as labour (contractions every 5 min associated with cervical dilatation) or non-labour. OTR mRNA expression was measured as optical density units from autoradiographs. There was a highly significant (P<0.001) effect of tissue type on expression of OTR mRNA with expression greatest in myometrium, low in decidua and chorion and not detected in placenta. Similar results were obtained with the 125I-OTA-binding studies, indicating that the message was translated. Amnion had an apparently high level of both hybridization and 125I-OTA binding in some samples, but a lack of specificity prevented quantification of the signal in this tissue type. Term myometrium (labour and non-labour) had significantly higher (P<0.01) OTR mRNA expression than preterm myometrium, but there was no further increase in mRNA concentration associated with labour onset. In contrast, 125I-OTA binding in myometrium was already high at 33 weeks and did not increase further either later in pregnancy or with labour. In decidua there was no effect of gestational age or labour onset on OTR mRNA expression or 125I-OTA binding. In summary, OTR mRNA expression in the myometrium increased in late pregnancy whereas decidual expression was much lower and did not rise at term. (+info)
Effect of sodium cloprostenol and flunixin meglumine on luteolysis and the timing of birth in bitches.
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At birth, the physiological role of prostaglandins in bitches is unclear. Bitches were treated before parturition with either saline, the prostaglandin analogue, sodium cloprostenol, or the prostaglandin synthetase inhibitor, flunixin meglumine. The animals were examined regularly to determine the onset of parturition and a series of blood samples were taken to define the hormonal profiles before, during and after birth. Animals treated with cloprostenol whelped earlier than did controls. In addition, the prostaglandin F2 alpha metabolite surge and decrease in plasma progesterone concentration and rectal temperature were earlier than in controls. Flunixin meglumine disrupted the normal 13,14-dihydro-15-keto prostaglandin F2 alpha profile but did not abolish prostaglandin synthesis completely or delay the onset of labour in treated animals. This study confirms that prostaglandins induce luteolysis and the onset of labour in the bitch. However, the partial inhibition of prostaglandin synthesis does not prevent parturition. (+info)
Differential regulation of prostaglandin EP and FP receptors in pregnant sheep myometrium and endometrium during spontaneous term labor.
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In the present study, we characterized the mRNA abundance of prostaglandin E(2) receptor subtypes (EP1 and EP3, which stimulate excitatory responses; EP2 and EP4, which stimulate inhibitory responses) and the FP receptor in pregnant sheep myometrium and endometrium in relation to parturition. Myometrial and endometrial poly(A) RNA was extracted from control ewes at 143-147 days gestational age (dGA, n = 6) and from ewes in spontaneous term labor at 145-147 dGA (n = 6), and was subjected to Northern blot analysis for FP, EP1, EP2, EP3, and EP4 mRNA. Myometrial EP3, EP4, and FP mRNA abundance increased during labor (P<0.05); EP2 mRNA did not change. EP1 mRNA was not detectable in the myometrium. Endometrial EP2 and EP4 mRNA remained unchanged during labor. EP3 mRNA was expressed at a very low level, and EP1 and FP mRNA were not detected in endometrium in any animals studied. In conclusion, there is differential expression in myometrium and endometrium of EP subtypes and FP receptor in relation to labor. Increases in EP3 and FP, together with increased prostaglandin production from intrauterine tissues, may lead to the switch in the myometrial contraction pattern that occurs during labor. These differences within and between myometrium and endometrium may result from different anatomical location, such as longitudinal or circular layers of myometrium, or vascular location. (+info)
Risk factors for 14-21 week abortions: a case-control study in Europe. The Europop Group.
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Data from a case-control survey in Europe, carried out between 1994 and 1997, were used to investigate the risk factors for spontaneous abortions at 14-21 weeks (late abortions), according to the vital status of the fetus before the onset of labour. Late abortions included 62 involving a fetus alive before the onset of labour, 216 late abortions of a fetus already dead, together with 4592 control pregnancies at term (>/=37 weeks) from seven countries. Histories of induced abortion, spontaneous abortion and preterm birth were more closely associated with late abortion of a live fetus than with late abortion of a dead fetus. Women aged >/=35 years and women living alone had a much higher risk of late abortions than women aged 20-24 years and married women, regardless of the vital status of the fetus before labour. These results provide evidence that obstetric history and socio-demographic factors are risk factors for late abortions but differences are observed according to the vital status of the fetus before labour. (+info)
Myosin light chain kinase and the onset of labour in humans.
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Myosin light chain kinase (MLCK) is essential for myometrial contractions induced by calcium-mobilizing agonists. From the gene of vertebrate smooth muscle/non-muscle MLCK there are at least four proteins expressed. We have found that both a > 200 and a 137 kDa MLCK are equally expressed in human non-pregnant (NP) and term pregnant (P) uterine smooth muscle and confirmed that 19 kDa telokin (TK) is only expressed in P myometrium. In addition, we have observed that a MLCK immunogen at approximately 60 kDa is only expressed in NP myometrium, suggesting that its expression is inhibited during normal pregnancy in a hormonally dependent manner. However, when we compared pregnant myometrium from patients delivered preterm (PT) (< 34 weeks gestation), but not in labour (NIL), with PT patients in labour (IL) we found that PT(IL) samples expressed the approximately 60 kDa MLCK immunogen and thus displayed a NP phenotype whereas PT(NIL) samples did not express the protein and retained a pregnant phenotype. We hypothesize that the novel approximately 60 kDa MLCK immunogen contributes to the aberrent contractility associated with preterm labour. Experimental Physiology (2001) 86.2, 313-318. (+info)
Uterine contraction pattern as a predictor of the mode of delivery.
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OBJECTIVE: To determine whether analysis of the frequency or regularity of uterine contractions can distinguish between women delivering vaginally and women requiring Cesarean section for dystocia. STUDY DESIGN: This was a case-control study. Cases meeting the following criteria were identified: nulliparous women in spontaneous labor, singleton pregnancy, cephalic presentation, 37 to 42 weeks' gestation, Cesarean section for dystocia, a minimum of three analyzable hours of electronically archived cardiotocograph (CTG) prior to onset of the second stage. Cases delivered by Cesarean section for dystocia were each matched with two controls delivering vaginally. The peak of each contraction was visually identified and electronically marked on each CTG trace. A moving average (MTIME) and standard deviation (SDTIME) of five interpeak times were calculated for successive 30-minute periods and plotted against cervical dilatation for each group. RESULTS: Overall, both MTIME and SDTIME fell as labor progressed, with these changes being more marked in the vaginal delivery group. In women requiring oxytocin, the rate of fall of MTIME and SDTIME was significantly greater following oxytocin in the group which subsequently delivered vaginally (slope of MTIME -2.71 pre-oxytocin and -28.95 post-oxytocin, p=0.0004; slope of SDTIME -0.44 and -6.44, p=0.0002). No such change was seen in the Cesarean section group. CONCLUSION: As normal labor progresses, there is a shortening of the intercontraction interval and an increase in contraction regularity. A successful response to oxytocin augmentation may be predicted by the change in contraction pattern following treatment. (+info)
Comparison of potassium currents in human decidua before and after the onset of labor.
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The human decidua plays a prominent role in the signaling between maternal and fetal tissues. It also secretes a plethora of molecules that modulate uterine function. Ion-channel activity underpins many cellular functions; however, the channels in human decidua have not been characterized in any detail. We have used the whole-cell recording mode of the patch-clamp technique to carry out current-clamp and voltage-clamp recordings of membrane properties and whole-cell potassium (K+) currents of freshly isolated decidual stromal cells. Decidual tissue was obtained from women after spontaneous vaginal delivery (SVD) or elective cesarean section (CS). Cells from both groups generated action potentials, the overshoots and durations of which were dependent on extracellular calcium levels, inhibited by cobalt and enhanced by barium. Potassium current (IK) density was higher in the CS than in the SVD group. Outwardly directed currents were heterogeneous with respect to their activation/inactivation profiles and exhibited outward rectification. The main difference between the SVD and CS group was the presence of a sustained current component in CS cells that is tetraethylammonium chloride-resistant and appears to be unaffected by E-4031. No evidence for the activation of any calcium-activated K+ currents was obtained. We propose that human parturition is associated with subtle changes in K+ channel remodeling, reflecting the transition from uterine quiescence to activation and stimulation. An understanding of the signal transduction events underlying these process may eventually lead to novel approaches to prevent preterm labor via decidual rather than myometrial intervention. (+info)