Increased placental expression of tissue factor is associated with abnormal uterine and umbilical Doppler waveforms in severe preeclampsia with fetal growth restriction (original) (raw)
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Laboratory Investigation
Failure of the placental capillary network to develop normally is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the symptoms are observed at term, the problem begins in the first trimester. However, investigations at this clinically relevant time are hindered by difficulties in identifying earlystage pregnancies that are at risk of developing FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy measure of poor placentation, we have identified pregnancies at increased risk of developing early onset FGR/PE. Placental endothelial cells (PEC) isolated from pregnancies at increased risk of developing FGR/PE grew more slowly and their basal rate of apoptosis was significantly higher than that seen in the normal group. The pro-apoptotic stimulus, TNFα, induced apoptosis in cells from both groups but this was significantly greater in the high risk group. TNF receptor expression was unaffected. Inhibition of nitric oxide (NO) production significantly increased the sensitivity of cells from the normal pregnancies to TNFα but not in the high risk group establishing a functional role for NO in this system. In conclusion, first trimester PEC from pregnancies at increased risk of developing early onset FGR/PE were inherently more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in on going pregnancies.
American Journal of Obstetrics and Gynecology, 2006
Objective: The purpose of this study was to evaluate possible relationships between placental markers and endothelial dysfunction in preeclampsia and intrauterine growth restriction. Study design: A prospective study was conducted in 76 patients with preeclampsia and 37 patients with intrauterine growth restriction that were classified as early onset (!34 weeks of gestational age) or late onset, and 40 control subjects. Plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, vascular cell adhesion molecule-1, and uterine artery Doppler indices were measured. Results: In early-onset preeclampsia and intrauterine growth restriction, placental growth factor was lower and soluble fms-like tyrosine kinase-1 and vascular cell adhesion molecule-1 higher than in control subjects, although all changes were more pronounced in preeclampsia. In lateonset preeclampsia, those patients with abnormal uterine artery Doppler indices had higher soluble fms-like tyrosine kinase-1 and vascular cell adhesion molecule-1 levels. Conclusion: Biochemical changes in early-onset preeclampsia and intrauterine growth restriction point to a common placental disorder and a state of endothelial dysfunction, which may require interaction with other factors to explain the maternal disease in preeclampsia. Data in late-onset preeclampsia suggest that a proportion of them may occur with minimal placental involvement.
Journal of Histochemistry and Cytochemistry, 2005
In the physiology of placental blood circulation, nitric oxide (NO) synthases seem to play important roles, although their expression in pathological placentas and their role is still unclear. In addition, NO synthase activation seems to be related to estrogen receptor expression. Therefore, the aims of this study were to investigate the expression of estrogen receptors alpha (ER ␣ ), estrogen receptor beta (ER and the endothelial NO synthase (eNOS), and inducible NO synthase (iNOS) in intrauterine growth-restricted (IUGR) placentas, preeclamptic placentas, and in normal healthy control placentas. Slides of paraffin-embedded placental tissue were obtained after delivery from patients diagnosed with IUGR, preeclampsia, and normal term placentas and analyzed for eNOS, iNOS as well as ER ␣ and ER  expression. Intensity of immunohistochemical reaction was analyzed using a semiquantitative score and statistical analysis was performed. In addition, Western blot experiments were performed for comparison of staining intensities obtained by immunohistochemistry and western blot. Expression of eNOS, iNOS, and ER  is significantly reduced in trophoblast cells of placentas with IUGR. However, preeclamptic placentas demonstrated a significant elevated expression intensity of these proteins compared with normal controls. A different expression of eNOS, iNOS, ER ␣ , and ER  by human trophoblast cells seems to results in lower NO output and impaired trophoblast invasion. Results obtained in our study provide evidence that reduced expression of the investigated proteins is related to IUGR. (J Histochem Cytochem 53:1441-1449, 2005) K E Y W O R D S nitric oxide synthases estrogen receptor alpha/beta intrauterine growth restriction preeclampsia
Hypertension in Pregnancy, 1999
Objective: We investigated the hypothesis that changes in blood flow in the uteroplacental and fetoplacental circulation in preeclampsia are associated with an abnormality of placental or uterine placental bed nitric oxide (NO) synthesis. Merhods: We measured pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries in 20 patients with preeclampsia and 14 healthy pregnant controls before elective cesarean section. During cesarean section, biopsies from the uterine placental bed and the placenta were taken and the nitric oxide synthase (NOS) activity was measured by the ['HI L-arginine-[ " H ] L-citrulline conversion assay in these samples. Results: The NOS activity was significantly lower in the uterine placental bed in comparison to the placental tissue (p < 0.01).
Journal of Pregnancy, 2012
Background. Poor placentation and systemic endothelial dysfunction have been identified as main events in Preeclampsia (PE). The relationship and chronology of these phenomena are important if we are to understand the pathophysiological mechanisms underlying this major clinical problem. Objectives. To compare the evolution of placentation and endothelial function in normotensive and preeclamptic pregnancies. Patients and methods. In a prospective cohort study, 59 pregnant women with a high risk of developing PE were subjected to flow-mediated dilation (FMD) and to Doppler velocimetry of uterine arteries in order to obtain their Pulsatility Index (UtA-PI). The variations in the FMD and UtA-PI values, between 16 +0 and 19 +6 and 24 +0 and 27 +6 weeks of gestation, were compared, taking PE development into consideration. Results. Nine patients developed PE and the other 50 women remained normotensive. At 16 +0 to 19 +6 weeks of pregnancy, patients that developed PE presented higher values of UtA-PI than the normotensive group, but there was no difference in FMD results between them. At 24 +0 to 27 +6 weeks, the patients that developed PE presented higher values of UtA-PI and lower values of FMD than the women that remained normotensive. Conclusions. These results corroborate the evidence that endothelial injury is secondary to poor placentation.