Human labour is associated with increased prostaglandin synthesis within the uterus. The aim of this study was to examine the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2) in human myometrium throughout pregnancy and to test the hypothesis that COX in the myometrium may play a role in labour onset. Expression of COX-1 and COX-2 at the mRNA level was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR) and at the protein level using Western blotting. No significant changes of COX-1 RNA or protein expression were observed either with gestational age or labour. COX-2 mRNA and protein expression increased at term with significant up-regulation occurring prior to the onset of labour (P < 0.005). These data would suggest that up-regulation of COX-2, rather than COX-1, mediates increased prostaglandin synthesis in human myometrium at term. The increased COX-2 expression observed preceded labour onset, suggesting that COX-2 has a role in labour onset, rather than its presence merely a consequence of labour.

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, cyclooxygenase (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.

Objective: Approximately 2.8% of pregnancies are Ro/La antibody positive. 3-15% of fetuses develop complete heart block (CHB). First-degree atrioventricular heart block (1˚AVB) is reported in a third of Ro/La fetuses but as most have a normal postnatal ECG this may reflect inadequacies of Doppler measurement techniques. Methods: Comparison was made between mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study at a fetal medicine unit. 121 mPR and 37 ePR intervals were recorded in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/37 (94%) and mPR was measured in all cases. 1˚AVB was defined as PR .95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR.Results: The ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases were predicted correctly in fetuses .20 weeks) and 96.2% specificity. mPR gave 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. The area under the receiver operator characteristic (ROC) curve was 0.88 (95% CI, 0.754 to 1.007). A cut-off of 1.65 gave a sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals, respectively. Conclusion: zPR is better than mPR at differentiating between normal and prolonged PR intervals, suggesting that fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies. A nti-Ro or La antibody positive pregnancies (Ro/La) have been found in about 2.8% of the pregnant population. The most serious consequence of transplacental transfer of these antibodies to the fetus is complete heart block (CHB), which affects 3% of Ro/La pregnancies, with the risk rising to 15% in a subsequent pregnancy. [1][2][3][4] In addition to the morbidity and mortality associated with pacing procedures in young infants, 5 6 progressive myocardial fibrosis has been reported which affects long-term cardiac function and may necessitate transplantation.7-9 The alloimmune process is thought to exert its effect in more than the 3% of fetuses affected by CHB with PR interval prolongation (first-degree atrioventricular heart block or 1˚AVB) described in up to a third of fetuses in studies using Doppler methods of measurement.10 As most babies have a normal outcome, with progression to CHB described in only a small proportion, there is some debate over whether these findings represent a transient biological response to the presence of antibodies or whether they may be due to inadequacies of the existing measurement techniques. 11A simple and robust method of monitoring the PR interval in affected pregnancies is required to enable studies to assess the extent and determinants of progression to CHB in Ro/La pregnancies. Such a tool would also permit the assessment of different trea...

Endogenous nitric oxide has been proposed to play a role in the control of myometrial contractility in pregnancy. In this study, the expression, localisation and regulation of nitric oxide synthase (NOS) isoforms have been examined in human pregnant myometrium and cultured human myometrial smooth muscle cells, by immunoblotting, immunohistochemistry and reverse transcription‐polymerase chain reaction. Immunoblotting of extracts from freshly isolated myometrial tissue, affinity‐enriched for NOS proteins by precipitation with ADP‐sepharose, revealed expression of endothelial NOS (eNOS or NOS3) in tissues from preterm, term non‐labour and active labour at term. Inducible NOS (iNOS or NOS2) and neuronal NOS (nNOS or NOS1) proteins were not detected at any stage of pregnancy. Immunohistochemical detection showed that expression of eNOS protein was restricted to the endothelium of the myometrial vasculature, with no staining detected in myometrial smooth muscle cells. Messenger RNA for all three NOS isoforms was detected, although iNOS and nNOS mRNAs were detectable only with high cycle number, implying a low copy number. NOS isoforms were not detectable in human myometrial smooth muscle cells cultured from term non‐labour pregnancies. Cytokine stimulation of cultured myometrial cells did not induce iNOS expression or nitrite accumulation in the culture medium, although both iNOS protein and nitrite release were detected in the human pulmonary epithelial cell line A549. Levels of eNOS protein and of NOS mRNA expression were not correlated with gestational stage, suggesting that endogenously produced NO is not likely to be a modulator of myometrial tone during human pregnancy.

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