Gene and protein expression in the myometrium in pregnancy and labor.
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Microarray technologies widen our comprehension of the major structural and metabolic transformations which affect the myometrium from the very beginning of pregnancy until parturition. The results are coherent with the mass of information which was accumulated previously, primarily on the basis of studies of selected critical factors. They highlight the activation of precise signaling pathways, some of which may have been previously under evaluated. The remodelling and maturation processes that the myometrium undergoes in pregnancy appear clearly as phenomena which last during the full course of gestation. Comparatively, the onset of labor is perhaps the phenomenon which remains the least well described by these methods of analysis. Nevertheless, genomic studies constitute a necessary first step of orientation and help establishing new links between the generic signaling pathways that are activated during the normal or pathological gestation. These studies also represent an indicative step that will have to be paralleled, in the future, with the results of the systematic proteomic analysis of the myometrium. (+info)
Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia.
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Elevated circulating levels of the tachykinin, neurokinin B (NKB), have been observed in women with pre-eclampsia during the third trimester of pregnancy. Currently, the molecular mechanisms responsible for these increased levels remain unknown. To understand the molecular regulation, we have compared the differences in gene expression of the tachykinins and their receptors in control and pre-eclamptic placentae and the responses of the TAC3 gene encoding NKB to proposed physiological triggers of pre-eclampsia including hypoxia and oxidative stress using real-time quantitative PCR. We have determined the placenta to be the main site of TAC3 expression with levels 2.6-fold higher than the brain. TAC3 expression was found to be significantly higher in pre-eclamptic placenta (1.7-fold, P < 0.05) than in normal controls. No evidence was found that hypoxia and oxidative stress were responsible for increases in TAC3 expression. In rat placenta, a longitudinal study in normal late pregnancy was associated with a significant down-regulation of the NKB/NK3 ligand-receptor pair (P < 0.05). The present data suggest that the increased placental expression of TAC3 is part of the mechanism leading to the increased circulating levels of NKB in pre-eclampsia. (+info)
Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal mass.
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Correlations between placental size and fetal mass during gestation fail to account for changes in composition that accompany placental growth and maturation. This study uses stereological data on the sizes of different tissue compartments in human placentas from 10 weeks of gestation to term and relates them to placental volume and to fetal mass by means of allometric analysis. In addition, tissue dimensions are used to calculate a physiological transport measure (diffusive conductance) for the villous membrane. Histological sections randomly sampled from placentas and analysed stereologically provided estimates of structural quantities (volumes, exchange surface areas, lengths, numbers of nuclei, diffusion distances). These data were combined with a physicochemical quantity (Krogh's diffusion coefficient) in order to estimate oxygen diffusive conductances for the villous membrane and its two components (trophoblast and stroma). Allometric relationships between these quantities and placental volume or fetal mass were obtained by linear regression analyses after log-transformation. Placental tissues had different growth trajectories: most grew more rapidly than placental volume and all grew more slowly than fetal mass. Diffusion distances were inversely related to placental and fetal size. Differential growth impacted on diffusive conductances, which, again, did not improve commensurately with placental volume but did match exactly growth of the fetus. Findings show that successful integration between supply and demand can be achieved by differential tissue growth. Allometric analysis of results from recent studies on the murine placenta suggest further that diffusive conductances may also be matched to fetal mass during gestation and to fetal mass at term across species. (+info)
Reference data representative of normal findings at three-dimensional power Doppler ultrasound examination of the cervix from 17 to 41 gestational weeks.
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OBJECTIVES: To develop normal reference ranges for cervical volume and vascular indices using three-dimensional (3D) power Doppler ultrasonography from 17 to 41 gestational weeks. METHODS: This was a cross-sectional study of 352 nulliparous and 291 parous women who delivered at term and underwent transvaginal 3D power Doppler ultrasound examination of the cervix once at 17 to 41 weeks' gestation. We examined approximately 25 women in each gestational week. Cervical volume, vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated. RESULTS: There was no change in cervical volume between 17 and 40 weeks' gestation. At 41 weeks cervical volume was slightly smaller than it was at 17-40 weeks (P=0.03 for nulliparous women and P=0.08 for parous women). The cervical volume was larger in parous than it was in nulliparous women (median 38 cm3 vs. 32 cm3 at 17-40 weeks, P<0.0001; median 31 cm3 vs. 22 cm3 at 41 gestational weeks, P=0.288). FI did not differ between nulliparous and parous women and remained unchanged between 17 and 41 weeks' gestation (median 30.6, range 21.2-55.2). VI and VFI did not change consistently from 17 to 41 weeks, but the values were higher in parous than they were in nulliparous women at 17-30 weeks (median VI 5.3% vs. 3.1%, P<0.0001; median VFI 1.6 vs. 0.9, P<0.0001). At 31-41 gestational weeks the median VI for all women irrespective of parity was 4.9% and the median VFI was 1.4. CONCLUSION: Reference values for cervical volume and blood flow indices as assessed by 3D power Doppler ultrasonography have been established for the second half of pregnancy. These lay the basis for studies of pathological conditions. (+info)
Fetal rhd genotyping from maternal plasma in a population with a highly diverse ethnic background.
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OBJECTIVE: To establish the performance of conventional PCR as a noninvasive method for fetal genotyping, by free fetal DNA analysis of distinct RHD regions from maternal plasma, in a population of a diverse ethnic origin. METHODS: We conducted a validity of the diagnostic test by analyzing 81 plasma samples from RhD-negative Brazilian pregnant women, from 4 to 41 gestational weeks. We tested for exon 10 and intron 4 gene regions by allele specific-PCR. Fetal RHD genotyping by PCR on maternal plasma was compared to serologic RhD typing in the neonatal period. RESULTS: Samples were obtained as follows: 15 in the 1st, 37 in the 2nd and 29 in the 3rd trimester. General accuracy was 97.3%, sensitivity of 98.3% and specificity of 93.8%. CONCLUSIONS: Conventional PCR is an accurate method for fetal RHD genotyping on maternal plasma, even in a population of mixed ethnic origin. (+info)
Maternal androgen and estrogen concentrations are not associated with blood pressure changes in uncomplicated pregnancies.
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Systolic blood pressure increase between the second and third trimester of pregnancy has been associated with a substantially reduced maternal breast cancer risk, and it has been suggested that elevated androgens mediate the association. Androgen and estrogen concentrations were measured in maternal serum collected in 86 uncomplicated, singleton pregnancies. Overall, there were no consistent or statistically significant patterns of association between the hormones and systolic, diastolic, or mean arterial blood pressure or blood pressure change between trimesters. Results were similar with adjustment for factors related to the hormones. These data are not consistent with the hypothesis that elevated androgen concentrations mediate the observed reduction in maternal breast cancer risk associated with increases in blood pressure over the pregnancy. (+info)
Left ventricular diastolic function during normal pregnancy: assessment by spectral tissue Doppler imaging.
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OBJECTIVE: Tissue Doppler imaging (TDI) is an echocardiographic technique for assessing the diastolic function that is relatively independent of preload. Since loading conditions change significantly during pregnancy, a load-independent technique will give a more accurate assessment of diastolic function in pregnant women. The aim of this study was to evaluate maternal diastolic function using tissue Doppler imaging. METHODS: This was a prospective observational study on 35 healthy pregnant women. M-mode, transmitral inflow (peak transmitral flow velocities during early diastole (E wave) and atrial contraction (A wave)) and TDI studies (peak myocardial velocities during early diastole (Em wave), during atrial contraction (Am wave) and peak systole in ejection phase (Sm)) were performed in each trimester and postpartum. The differences in variables between trimesters were analyzed. RESULTS: The peak transmitral inflow velocity during early diastole (E wave) was significantly decreased during the third trimester and postpartum. The peak flow velocity during atrial contraction (A wave) was increased in the second trimester, but decreased again in the third trimester and postpartum period. As a result, the E/A ratio progressively reduced as pregnancy advanced. TDI showed that peak myocardial velocities during early diastole (Em) tended to increase during the second trimester, and then decreased significantly in the third trimester or postpartum period. The peak myocardial velocities during atrial contraction (Am) increased significantly with advancing gestational age. As a consequence, both Em/Am and E/Em ratios decreased significantly throughout pregnancy. CONCLUSIONS: This study demonstrates the changes in myocardial relaxation velocity throughout pregnancy. Because of its advantage of being relatively load-independent, TDI may be a useful non-invasive technique for monitoring maternal cardiac function in high-risk pregnancies to detect the early signs of cardiac failure and to prevent further deterioration with prompt interventions. (+info)
Lipid profile during pregnancy in HIV-infected women.
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PURPOSE: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. METHOD: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (PIs) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. RESULTS: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p < .001), 60.8 mg/dL for total cholesterol (p < .001), 13.7 mg/dL for HDL cholesterol (p < .001), and 17.8 mg/dL for LDL cholesterol (p = .001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on PIs. The effect of PIs on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. CONCLUSION: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV. (+info)