Alteration of calcium homeostasis in primary preeclamptic syncytiotrophoblasts: effect on calcium exchange in placenta (original) (raw)
Related papers
Placental oxidative stress: From miscarriage to preeclampsia
Journal of the Society for Gynecologic Investigation, 2004
To review the role of oxidative stress in two common placental-related disorders of pregnancy, miscarriage and preeclampsia. METHODS: Review of published literature. RESULTS: Miscarriage and preeclampsia manifest at contrasting stages of pregnancy, yet both have their roots in deficient trophoblast invasion during early gestation. Early after implantation, endovascular trophoblast cells migrate down the lumens of spiral arteries, and are associated with their physiological conversion into flaccid conduits. Initially these cells occlude the arteries, limiting maternal blood flow into the placenta. The embryo therefore develops in a low oxygen environment, protecting differentiating cells from damaging free radicals. Once embryogenesis is complete, the maternal intervillous circulation becomes fully established, and intraplacental oxygen concentration rises threefold. Onset of the circulation is normally a progressive periphery-center phenomenon, and high levels of oxidative stress in the periphery may induce formation of the chorion laeve. If trophoblast invasion is severely impaired, plugging of the spiral arteries is incomplete, and onset of the maternal intervillous circulation is premature and widespread throughout the placenta. Syncytiotrophoblastic oxidative damage is extensive, and likely a major contributory factor to miscarriage. Between these two extremes will be found differing degrees of trophoblast invasion compatible with ongoing pregnancy but resulting in deficient conversion of the spiral arteries and an ischemia-reperfusiontype phenomenon. Placental perfusion will be impaired to a greater or lesser extent, generating commensurate placental oxidative stress that is a major contributory factor to preeclampsia.
Hypoxia and reoxygenation: a possible mechanism for placental oxidative stress in preeclampsia
Taiwanese journal of obstetrics & gynecology, 2006
Preeclampsia is a human pregnancy-specific disorder that is diagnosed by the new appearance of hypertension and proteinuria after 20 weeks' gestation. It is a leading cause of perinatal morbidity and mortality, and the only intervention that effectively reverses the syndrome is delivery. Oxidative stress of the placenta is considered to be a key intermediary step in the pathogenesis of preeclampsia, but the cause for the stress remains unknown. Hypoxia-reoxygenation (H/R) injury, as a result of intermittent placental perfusion secondary to deficient trophoblast invasion of the endometrial arteries, is a possible mechanism. In this review, we present evidence to show that there is a plausible basis from which to assume that blood flow in the intervillous space will be intermittent in all normal pregnancies. The intermittency will be exacerbated by impaired conversion of the spiral arteries, or by the presence of atherotic changes that reduce their caliber as seen in preeclampsia....
2001
Pre-eclampsia (PE) is a life-threatening complication of pregnancy and one of the leading causes of maternal and fetal morbidity and mortality in the Western world, with early delivery as the only effective treatment. Increasing evidence implicates placental lipid peroxidation products as mediators of vascular endothelial and smooth muscle cell dysfunction, resulting in elevated blood pressure in women with PE. As PE is strongly associated with an abnormal development of the fetal circulation leading to fetal high resistance and hypoxic conditions, this research project aims to elucidate the cellular mechanisms mediating PE-induced abnormalities in the regulation of intracellular Ca 2+ ([Ca 2+ ] i), cyclic GMP production and ion channel activity in fetal endothelial and smooth muscle cells. This study has identified abnormalities in basal and histamine-stimulated [Ca 2+ ] i levels in human umbilical vein endothelial cells (HUVEC) from PE pregnancies, with a significantly decreased Ca 2+ entry in PE HUVEC. Moreover, basal [Ca 2+ ] i levels were significantly elevated in endothelial cells derived from PE pregnancies. Furthermore, entry of Mn 2+ was increased in HUVEC from PE pregnancies, and cells exhibited an altered permeability favouring ions such as Mn 2+ and Gd 3+ over Ca 2+ and Ba 2+. When basal [Ca 2+ ] i and intracellular cGMP levels were correlated in HUVEC, cells from PE pregnancies (~34 weeks gestation) exhibited significantly higher basal [Ca 2+ ] i and cGMP levels compared to cells from normal term or pre-term pregnancies of comparable gestational age. Western blot analyses revealed no significant differences in eNOS or sGC protein expression in HUVEC from normal, pre-term or pre-eclamptic pregnancies. Basal and histamine-stimulated rates of PGI 2 production were similar in normal and pre-eclamptic HUVEC. Arachidonic acid, an -unsaturated fatty acid and precursor for F 2isoprostanes, induced significantly greater increases in [Ca 2+ ] i in human umbilical artery smooth muscle cells (HUASMC) from PE pregnancies. Although arachidonic acid evoked [Ca 2+ ] i increases in HUVEC, no differences between normal and PE cells were found. The greater [Ca 2+ ] i increases in PE HUASMC could be mimiced in normal cells by incubation with indomethacin, an inhibitor of cyclooxygenase. Increases in [Ca 2+ ] i in responses to oleic acid and linoleic acid were smaller and not different between normal and PE HUASMC. Cyclooxygenase-1 (COX-1) levels were generally downregulated in PE HUASMC.
Placenta, 2009
The pregnancy complications of unexplained intrauterine growth restriction and early onset preeclampsia are thought to share a common aetiology in placental malperfusion secondary to deficient maternal spiral artery conversion. A key question is whether the contrasting clinical manifestations reflect different placental pathologies, or whether they are due to altered maternal responses to a common factor derived from the placenta. Recently, molecular evidence of protein synthesis inhibition secondary to endoplasmic reticulum stress has provided an explanation for the small placental phenotype in both conditions. However, other pathways activated by more severe endoplasmic reticulum stress are only observed in placentas from pregnancies associated with early onset preeclampsia. Here, we review the literature and conclude that there is evidence of greater maternal vascular compromise of the placenta in these cases. We speculate that in cases of normotensive intrauterine growth restriction the placental pathology is centred predominantly around endoplasmic reticulum stress, whereas in cases complicated by preeclampsia oxidative stress is further superimposed. This causes the release of a potent mix of pro-inflammatory cytokines, antiangiogenic factors and trophoblastic aponecrotic debris into the maternal circulation that causes the peripheral syndrome. Maternal and fetal constitutional factors may modulate how the placenta responds to the maternal vascular insult, and how the mother is affected by the placental factors released. However, the principal conclusion is that the difference between these two conditions lies in the severity of the initiating deficit in spiral arterial conversion, and the relative degrees of endoplasmic reticulum stress and oxidative stress induced in the placenta as a result.
Redox Modulation of Ca 2+ Signaling in Human Endothelial and Smooth Muscle Cells in Pre-Eclampsia
Antioxidants & Redox Signaling, 2009
Pre-eclampsia (PE) is a leading cause of maternal hypertension in pregnancy and is associated with fetal growth restriction, premature birth, and fetal and maternal mortality. Activation and dysfunction of the maternal and fetal endothelium in PE appears to be a consequence of increased oxidative stress, resulting from elevated levels of circulating lipid peroxides. Accumulating evidence implicates reactive oxygen species (ROS) in the pathogenesis of vascular dysfunction in PE, perhaps involving a disturbance in intracellular Ca 2+ signaling. Several ion-transport pathways are highly sensitive to oxidative stress, and the resulting modulation of ion transport by ROS will affect intracellular Ca 2+ homeostasis. We review the evidence that changes in ion transport induced by ROS may be linked with abnormalities in Ca 2+ -mediated signal transduction, leading to endothelial and smooth muscle dysfunction in maternal and fetal circulations in PE. As dysregulation of Ca 2+ signaling in fetal umbilical endothelial cells is maintained in culture and embryonic, fetal, and postnatal development is affected by the cellular redox state, we hypothesize that impaired redox signaling in PE may influence ''programming'' of the fetal cardiovascular system and endothelial function in adulthood. Antioxid. Redox Signal. 11, 0000-0000.
Oxidative Stress in Preeclampsia and Placental Diseases
International journal of molecular sciences, 2018
Preeclampsia is a persistent hypertensive gestational disease characterized by high blood pressure and proteinuria, which presents from the second trimester of pregnancy. At the cellular level, preeclampsia has largely been associated with the release of free radicals by the placenta. Placenta-borne oxidative and nitrosative stresses are even sometimes considered as the major molecular determinants of the maternal disease. In this review, we present the recent literature evaluating free radical production in both normal and pathological placentas (including preeclampsia and other major pregnancy diseases), in humans and animal models. We then assess the putative effects of these free radicals on the placenta and maternal endothelium. This analysis was conducted with regard to recent papers and possible therapeutic avenues.
IFPA Senior Award Lecture: Making sense of pre-eclampsia – Two placental causes of preeclampsia?
Placenta, 2014
Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation.
The Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction
Annals of the New York Academy of Sciences, 2008
Preeclampsia is associated with an increased release of factors from the placental syncytium into maternal blood, including the antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluable endoglin, the antifibrinolytic factor plasminogen activator inhibitor-1, prostanoids, lipoperoxides, cytokines, and microparticles. These factors are suggested to promote maternal endothelium dysfunction and are associated with placental damage in pregnancies also complicated with intrauterine growth restriction (IUGR). In this report, we briefly describe the interaction of syncytial factors with hypoxia, reactive oxygen species, and apoptosis in the pathophysiology of preeclampsia and IUGR. Given the critical role of the syncytium in these complications of pregnancy, we also present a novel methodology in which laser capture microdissection followed by Western blotting is used to assess levels of syncytial Fas ligand, a key protein in the apoptotic cascade.