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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prenatal diagnosis of fetal genetic conditions is a standard part of modern obstetric care. Many of the current methods rely on invasive methods and are associated with an inherent risk of fetal loss. Consequently, there has been a long-term goal for development of noninvasive prenatal diagnostic methods. In 1997, the presence of fetal DNA in maternal plasma was first discovered through the detection of Y-chromosome-specific sequences in the plasma of women conceived with male fetuses. This discovery has opened up new possibilities in the development of noninvasive prenatal diagnostic methods through a source of fetal genetic material that could be conveniently accessible simply through the collection of a maternal peripheral blood sample. To date, there have been numerous reported applications, including fetal RhD genotyping, prenatal diagnosis of sex-linked disorders, paternally inherited genetic diseases and some pregnancy-associated conditions, including preeclampsia. More recently, there have been significant new developments with expanding number of potential applications.
Expert Rev Mol Diagn 2002 Jan
PMID:Application of fetal DNA in maternal plasma for noninvasive prenatal diagnosis. 1196

Conversion of the maternal spiral arteries into larger competent vessels is one of the essential steps in the development of the normal placenta. This process is apparently dependent on the invasion by trophoblasts of the sub-endometrial area and the spiral arteries. Preeclampsia is characterized by shallow trophoblast invasion and unconverted narrow spiral arteries. This leads to fetal hypoxia that causes endothelial injury that eventually manifest as maternal hypertension, edema, and proteinuria. The following steps have been shown to be involved in the breakthrough of the trophoblasts from the uterine cavity into the decidua and the spiral arteries: trophoblast targeting, adhesion, and detachment from the extracellular matrix (ECM), invasion of the ECM and maternal vessels by proteolysis. Abnormal expression and activity of these molecules may explain in part some of the molecular mechanisms leading to abnormal placentation and the development of preeclampsia.
Mol Cell Endocrinol 2002 Feb 22
PMID:Regulation of trophoblast invasion: from normal implantation to pre-eclampsia. 1198 32

Susceptibility genes present in both mother and fetus most likely contribute to the risk of pre-eclampsia. Placental biopsies were therefore investigated by high-density DNA microarray analysis to determine genes differentially regulated within chorionic villous tissue in pre-eclampsia and normal pregnancy. The pooled RNAs of pre-eclamptic and normotensive subjects were hybridized to the HuGeneFL array representing sequences from approximately 5600 full-length human cDNAs. The differentially expressed genes that were detected could be categorized into nine groups: adhesion molecules, obesity-related genes, transcription factors/signalling molecules, immunological factors, neuromediators, oncogenic factors, protease inhibitors, hormones and growth factor-binding proteins. Among those, the obesity-related genes included putative candidate genes associated with the pathogenesis of pre-eclampsia. One of the most up-regulated transcripts was the obese gene (43.6-fold change), and this was reflected by elevated leptin protein levels. In the case of feto-maternal contribution of polymorphic genes to pre-eclampsia, expression analysis of placental tissue has lead to numerous target genes waiting for large scale genetic linkage analyses.
Mol Hum Reprod 2002 Jul
PMID:Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes. 1208 83

Fetal cells, specifically fetal erythroblasts, as well as cell-free fetal DNA are present in the maternal circulation. Both are currently being investigated as a means for the non-invasive risk-free analysis of fetal genetic traits. The origin of this cell-free fetal DNA in the maternal circulation is currently unclear. Since numerous fetal erythroblasts have been demonstrated to exhibit an apoptotic phenotype in the form of fragmented nuclear DNA, it has been proposed that such trafficking fetal cells may be a possible source. This hypothesis is supported by reports of elevated numbers of fetal erythroblast and cell-free fetal DNA concentrations in pregnancies affected by pre-eclampsia or polyhydramnios. To address this question, we have examined fetal erythroblast numbers and cell-free DNA concentrations in the same maternal blood samples. Our study, performed on both normal and pathologically-affected pregnancies, indicates that no correlation exists between these two fetal cellular and molecular species. This is most evident in pregnancies affected by onset of preterm labour, where significant elevations in cell-free fetal DNA concentrations were detected without any concomitant elevation in fetal erythroblast numbers. Our data therefore suggest that an alternative cell type is the source of cell-free fetal DNA. Furthermore, it appears that the release of cell-free fetal DNA from this cell type is affected by pathological placental conditions which are not associated with an increase in fetal cell trafficking.
Mol Hum Reprod 2002 Sep
PMID:Cell-free fetal DNA in the maternal circulation does not stem from the transplacental passage of fetal erythroblasts. 1220 Apr 65

Pre-eclampsia, is the most common, pregnancy-associated pathological syndrome accompanied by a significant increase in collagen and sulphated glycosaminoglycans (GAGs) contents in the umbilical cord arteries (UCAs). Insulin-like growth factor-I (IGF-I) is expressed in most foetal tissues and it is involved in anabolic effects. It stimulates protein (mainly collagen) and GAG biosynthesis, cell proliferation and differentiation. Previously, we have found that pre-eclampsia is associated with an increase of IGF-I concentration in the umbilical cord blood. A family of IGF-I-binding proteins (BPs) modulates the activity of IGF-I. We demonstrated qualitative differences between BPs of normal and pre-eclamptic human umbilical cord (UC) serum and UC-tissues (UCA-wall and Wharton's jelly) by Western immunoblot analysis. All examined sera and tissues contained BP-1 and BP-5 as well lower molecular weight materials. The BP-2 was recovered from both control and pre-eclamptic sera, while it was not detected in the UC-tissues. Instead, lower molecular weight forms of BP-2 were found as judged by the anti-BP-2 antibody. The BP-3 was detected in sera, UCA and Wharton's jelly. The most distinct expression of BP-3 was found in the UCA. The pre-eclamptic UCA and Wharton's jelly contained additional BP-3-reactive material of lower molecular weight. The BP-4 was strongly expressed in pre-eclamptic UC-serum and the expression was decreased in pre-eclamptic UC-tissues, compared to respective controls. Ligand binding assay revealed that most of IGF-I was bound to 46 kDa region (typical for BP-3) in both control and pre-eclamptic sera and tissues. However, distinctly less IGF-I was bound in pre-eclamptic serum, distinctly more in pre-eclamptic UCA and no differences were found in pre-eclamptic Wharton's jelly, compared to controls. We demonstrated that both normal and pre-eclamptic UC-sera and tissues are able to degrade 46 kDa IGF-I-BP. The degradation may result in a decrease of IGF-I binding, contributing to increase in free IGF-I that may stimulate the cells to produce extracellular matrix (ECM) components. The specific BPs and their proteolytic modification in UC tissues may be important modulators of IGF-I action during foetal development.
Mol Cell Biochem 2002 Aug
PMID:An expression of IGF-binding proteins in normal and pre-eclamptic human umbilical cord serum and tissues. 1223 78

p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display symptoms similar to preeclampsia. p57-/+ (heterozygotes for p57Kip2 ) female mice that were mated with p57-/+ males showed hypertension, proteinuria, thrombocytopenia, decreased anti-thrombin III activity, and increased endothelin levels during late pregnancy. In their kidneys, endotheliosis of glomeruli were recognized along with fibrinoid or hyalinoid deposits. These characteristics were also observed in pregnant p57-/+ females that were mated with wild type males, but not in pregnant wild type females mated with p57-/+ males or wild type males. The pregnant p57-/+ mice had conceptuses both with and without p57Kip2 expression. The conceptuses without p57Kip2 expression showed trophoblastic hyperplasia, which mimics the hallmark proliferation of intermediate trophoblasts in clinical preeclampsia. It is suggested that the preeclampsia-like symptoms of the pregnant p57-/+ mice might have been induced by the conceptus(es) without p57Kip2 expression. In addition, pregnant p57-/+ mice might serve as a new animal model for preeclampsia characterized by trophoblastic hyperplasia.
Mol Hum Reprod 2002 Dec
PMID:Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice. 1246 47

Human essential hypertension is a complex, multifactorial, quantitative trait under polygenic control. Although the exact etiology is unknown, the fundamental hemodynamic abnormality in hypertension is increased peripheral resistance, due primarily to changes in vascular structure and function. These changes include arterial wall thickening, abnormal vascular tone and endothelial dysfunction and are due to alterations in the biology of the cellular and non-cellular components of the arterial wall. Many of these processes are influenced by magnesium. Small changes in magnesium levels may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Accordingly magnesium may be important in the physiological regulation of blood pressure whereas perturbations in cellular magnesium homeostasis could play a role in pathophysiological processes underlying blood pressure elevation. For the most part, epidemiological and experimental studies demonstrate an inverse association between magnesium and blood pressure and support a role for magnesium in the pathogenesis of hypertension. However data from clinical studies have been less convincing and the therapeutic value of magnesium in the prevention and management of essential hypertension remains unclear. In view of the still ill-defined role of magnesium in clinical hypertension, magnesium supplementation is advised in those hypertensive patients who are receiving diuretics, who have resistant or secondary hypertension or who have frank magnesium deficiency. A magnesium-rich diet should be encouraged in the prevention of hypertension, particularly in predisposed communities because of the other advantages of such a diet in prevention. The clinical aspect that has demonstrated the greatest therapeutic potential for magnesium in hypertension, is in the treatment of pre-eclampsia and eclampsia. The present review discusses the role of magnesium in the regulation of vascular function and blood pressure and the implications in mechanisms underlying hypertension. Alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic actions of magnesium will also be addressed.
Mol Aspects Med
PMID:Role of magnesium in the pathogenesis of hypertension. 1253 92

Pre-eclampsia, or pregnancy-induced hypertension, is a major cause of maternal and fetal morbidity and mortality complicating 7-10% of pregnancies. Although mechanisms underlying pre-eclampsia are not well understood, endothelial dysfunction is considered to underscore many of the pre-eclamptic manifestations including hypertension, proteinuria and edema. Leptin, the obese gene product from adipocytes, is produced by the placenta during pregnancy. Serum leptin levels are elevated under normal pregnancy especially during the second trimester, which rapidly decreases and returns to normal after delivery, indicating the role of leptin as a gestational hormone for energy balance. Recent studies have revealed that the placental production of leptin may be pathologically augmented under pre-eclampsia although conflicting data also have been reported. Nevertheless, hyperleptinemia and possible further augmentation under pre-eclampsia may predispose to the development of maternal leptin resistance, which may be a component of insulin resistance predisposing the onset of endothelial dysfunction. This review summarizes recent findings regarding the putative changes of serum leptin levels during pre-eclampsia and the potential consequences on the vascular system.
Cell Mol Biol (Noisy-le-grand) 2002
PMID:Leptin, leptin resistance and endothelial dysfunction in pre-eclampsia. 1264 50

The objective of this study was to quantify the relative expression of inhibin alpha, inhibin/activin beta(A), beta(B), beta(C), follistatin, activin receptors and beta-glycan genes in placental tissue of term pre-eclamptic patients and controls to investigate if these genes are up-regulated in the placenta in pre-eclampsia. Seven women with pre-eclampsia symptoms were matched with 10 normal pregnant controls for gestational age, maternal age, and parity. Total RNA was isolated from each sample. Complementary DNA samples produced by reverse transcription were used in the real time PCR to quantify the expression of inhibin alpha subunit, inhibin/activin beta(A), beta(B), beta(C) subunits, follistatin, ACTRIA, ACTRIB, ACTRIIA, ACTRIIB, beta-glycan and GAPDH genes. The ratio between the target and GAPDH expression was calculated to provide relative gene expression. Inhibin alpha:GAPDH and inhibin/activin beta(A): GAPDH ratios were significantly higher in placental tissue from women with pre-eclampsia (P = 0.04 and P = 0.01 respectively) compared with matched control placental gene expression. Placental samples from both groups expressed beta(B), beta(C), follistatin, activin receptors and beta-glycan genes. However, there was no significant difference in the relative expression of these genes between the groups. Increases in the placental expression of inhibin alpha and inhibin/activin beta(A) subunit genes could contribute to the rise in circulating levels of inhibin A and activin A in pre-eclampsia. The mechanism(s) involved in increased gene expression in pre-eclampsia is as yet unclear.
Mol Hum Reprod 2003 Apr
PMID:Inhibin, activin, follistatin, activin receptors and beta-glycan gene expression in the placental tissue of patients with pre-eclampsia. 1265 1

Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre-eclampsia. Defining the physiological and pathological role of the fgl2/fibroleukin gene required an fgl2-knockout mouse and data on normal pattern of fgl2 expression during pregnancy. Expression of fgl2 protein was determined by immunostaining with specific antibody. Fgl2 knockout mice were generated and typed by PCR for presence of the altered gene. Immunostaining of timed CBAxDBA/2 mouse matings in a low-abortion-rate colony showed a distinct pattern of development of fgl2 protein expression in maternal decidua, and in embryonic tissues in early pregnancy. Outbred (mixed background) heterozygous fgl2 +/-x+/- matings with a similar low abortion rate showed selective occult loss of both +/- and, to a greater extent, -/- embryos prior to gestation day 11.5, in association with haemorrhage at the anti-mesometrial pole of fgl2-deficient embryo. LPS injected on day 6.5 caused classical abortions at mid-pregnancy in fgl2 +/+x+/+ matings, but not -/-x-/- matings. Physiological expression of fgl2 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fgl2 expression is required for LPS to induce abortion pathology.
Mol Hum Reprod 2004 Feb
PMID:The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction. 1474 94


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