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Most research on the developmental origins of health and disease has implicated poor nutrition in the fetus, most often conferred by deficiencies in maternal nutrition, as an important causal factor that programmes offspring physiology for adult disease. Emerging evidence implicates interactions between genes and the environment that may help to explain why poor growth before birth is associated with...
Preeclampsia is a complex disease of pregnancy with both feto-placental and maternal factors contributing to its pathogenesis. Failed transformation of the uterine spiral arteries leading to release of ischemic placental factors into the maternal circulation is thought to be the initial step in triggering preeclampsia. One placental factor associated with preeclampsia is necrotic trophoblastic debris...
Intra-uterine growth restriction (IUGR) is defined by a restriction of fetal growth during gestation. It is a prevalent significant public health problem that jeopardizes neonatal health but also that can have deleterious consequences later in adult life.Cullins constitute a family of seven proteins involved in cell scaffold and in selective proteolysis via the ubiquitin-proteasome system. Most Cullins...
Common complications of pregnancy arise in part from dysfunctional placental development, and include gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Peroxisome proliferator-activated receptors (PPARs), and their partner retinoid X receptor a (RXRα), mediate trophoblast differentiation and thus may offer insight into the pathophysiology of these diseases...
Many genes exhibiting genomic imprinting, parent-of-origin differences in gene expression, are involved in regulating placental and fetal growth. The goal of the present study was to assess whether abnormal regulation of imprinted genes is associated with intrauterine growth restriction (IUGR) and/or preeclampsia (PET).Genomic DNA was extracted from at least two whole villi samples from control (N=22),...
The pathophysiology of preeclampsia includes an unbalanced syncytiotrophoblast renewal from the underlying cytotrophoblast and increased necrotic/aponecrotic shedding of syncytiotrophoblast particles into the maternal circulation. These non-apoptotic syncytiotrophoblast fragments cause the maternal endothelial dysfunction underlying the syndrome of preeclampsia. In order to understand the pathophysiological...
A decreased antioxidant activity for superoxide dismutases (SODs) in the placenta was reported in preeclampsia (PE). However, it is unclear if this reduced enzymatic activity can be attributed to a specific SOD isoform. Moreover, the specific spatial SOD expression in the placenta and the impact of the mode of delivery on the latter are still lacking. There are three known SOD isoforms: SOD1 (cytosolic),...
Preeclampsia is a pregnancy-specific condition affecting 2–7% of women and a leading cause of perinatal and maternal morbidity and mortality; it may also predispose the mother and fetus to increased risks of adult cardiovascular disease. The selenoprotein glutathione peroxidases (GPxs) have critical roles in regulating antioxidant status.Immunohistochemical measurements of GPx1, GPx3 and GPx4 protein...
Preeclampsia is one of the leading causes for maternal and fetal morbidity. Placental protein 13 (PP13) is a placenta specific protein and with its decreased maternal serum levels in the first trimester it is one of the most promising markers to predict the syndrome in early pregnancy. In clinical trials attempts to prevent preeclampsia have already been made using low-dose aspirin, low-molecular-weight...
Increased placental release of soluble VEGF receptor-1 (sFlt-1) is believed to play an important role in the pathogenesis of preeclampsia (PE). Although the reason for increased placental sFlt-1 release in PE is unknown, proteolytic effect has been proposed as one of the mechanisms that mediate sFlt-1 release in the placenta. In this study, using various protease inhibitors, we tested the possible...
The complement system protects the host against invading organisms, initiates inflammation and dispose of immune complexes and the products of inflammatory injury. The complement system provides an important link between the innate and adaptive immune systems. Experimental observations suggest that increased complement activation causes and/or perpetuates inflammation during pregnancy. Recent studies...
Preeclampsia is a pregnancy-specific disorder associated with hyperlipidemia. Liver X receptor (LXR) α and LXRβ are key regulators of lipid homeostasis. In the current study, we investigated expression of LXRα, LXRβ and their target genes in human term placenta, decidua and subcutaneous adipose tissue from pregnancies complicated by preeclampsia. Furthermore, we analyzed the protein levels of LXRα...
Preeclampsia (PE) is a serious disorder of human pregnancy, it is often associated with fetal growth restriction (FGR) which is a failure of the fetus to reach its own growth potential.Activator protein-1 (AP-1) is a family of transcription factors inducible in response to a variety of extracellular stimuli and functions. AP-1 plays a complex role in the regulation of different fundamental cellular...
The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in the human placenta under normal physiological circumstances and in preeclampsia.We investigated the expression pattern...
The pathogenesis of preeclampsia is not clear but the disease is characterised by systemic endothelial cell dysfunction that is considered to be triggered by a placental factor. Necrotic trophoblastic debris that is deported in the maternal blood is one possible placental trigger for preeclampsia. Syncytial knots were first associated with preeclampsia over 100 years ago. However, syncytial knots...
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