[show abstract][hide abstract] ABSTRACT: The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n = 16) versus normal placentas (n = 16). Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p = 0.001), the binding sites of Sp1 (p = 1.57×10(-4)), LP1 (p = 0.023) and CEBPα (p = 0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBPα co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p = 1.57×10(-4)), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation.
PLoS ONE 01/2013; 8(3):e59753. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to identify candidate protein biomarkers from maternal serum for Down syndrome (DS) by integrated proteomic and bioinformatics analysis.
A pregnancy DS group of 18 women and a control group with the same number were prepared, and the maternal serum proteins were analyzed by isobaric tags for relative and absolute quantitation and mass spectrometry, to identify DS differentially expressed maternal serum proteins (DS-DEMSPs). Comprehensive bioinformatics analysis was then employed to analyze DS-DEMSPs both in this paper and seven related publications.
Down syndrome differentially expressed maternal serum proteins from different studies are significantly enriched with common Gene Ontology functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, transcription factor binding sites, and Pfam protein domains, However, the DS-DEMSPs are less functionally related to known DS-related genes. These evidences suggest that common molecular mechanisms induced by secondary effects may be present upon DS carrying. A simple scoring scheme revealed Alpha-2-macroglobulin, Apolipoprotein A1, Apolipoprotein E, Complement C1s subcomponent, Complement component 5, Complement component 8, alpha polypeptide, Complement component 8, beta polypeptide and Fibronectin as potential DS biomarkers.
The integration of proteomics and bioinformatics studies provides a novel approach to develop new prenatal screening methods for noninvasive yet accurate diagnosis of DS.
[show abstract][hide abstract] ABSTRACT: Disruption of the Catechol-O-methyltransferase (COMT) gene has been shown to be involved in pre-eclampsia (PE). To investigate whether two promoters of the COMT gene are differentially regulated by methylation in PE patients, we have analyzed the genomic DNA extracted from placenta (cases n = 16; controls n = 21), maternal peripheral blood (cases n = 4; controls n = 6) and umbilical cord blood (cases n = 8; controls n = 8) of women with PE and women with normal pregnancy. Bisulfite sequencing identified the predominantly unmethylated MB-COMT promoter in placenta, maternal peripheral blood and umbilical cord blood samples (PE and control). Subsequent quantitative MassArray data confirmed a significant tissue-specific hypomethylation of the S-COMT promoter in placenta (mean = 28.6%) when compared with its densely methylated patterns in blood samples (mean = 74.5%, P < 0.001), consistent with the sequencing data. However, no PE-specific methylation difference was found between cases and controls either in placenta or in blood samples. Moreover, none of the clinical characteristics had an effect on the methylation status of the S-COMT promoter. This study does not support a causal link between methylation regulation of COMT promoters and PE. However, the observed placenta-specific S-COMT promoter may be a potential marker for early prediction of PE in maternal plasma, although this remains to be further evaluated.
Molecular Human Reproduction 11/2010; 17(3):199-206. · 4.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cytotrophoblast cell differentiation into syncytiotrophoblast cells is a complex and delicate process, and the mechanism needs a large number of further studies. Knockout of 14-3-3τ expression and some further investigations were performed in the syncytiotrophoblast cell formation with RNA interference (RNAi) technology. The study found that the 14-3-3τ expression level with the formation of syncytiotrophoblast cells increased. Hypoxia inhibited the formation of syncytiotrophoblast cells where 14-3-3τ expression level decreased. RNAi reduced 14-3-3τ expression, and reduced the formation of syncytiotrophoblast cells. So that 14-3-3τ is not only involved in the cell regulation, but also in the formation of syncytiotrophoblast cells. 14-3-3τ is an important regulatory factor which inhibits the formation of hypoxia.
The Analyst 11/2010; 136(2):401-6. · 4.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: To elucidate the main source of circulating visfatin and its potential roles in pathogenesis of gestational diabetes mellitus (GDM).
We examined serum concentrations of visfatin with ELISA and its expression in subcutaneous adipose tissue, visceral adipose tissue and placenta with RT-PCR and western blot both in women with GDM and normal pregnant controls at term. Moreover, BeWo cells were treated with tumor necrosis factor-alpha (TNF-alpha) and then the intra- and extra-cellular changes of visfatin expression were measured.
Serum visfatin concentrations were significantly higher in women with GDM than controls, which reduced obviously three days after delivery compared with antepartum. Visfatin expressions in placenta were significantly higher in GDM women than controls but there was no difference in its expressions in adipose tissue between the two groups. Moreover, serum visfatin concentrations correlated positively with its expressions in placenta, rather than adipose tissue. We demonstrated that visfatin secretion from BeWo cells was significantly increased but the intracellular expression was decreased at 48h incubation with TNF-alpha in a dose-depended way.
The oversecretion of visfatin from placenta, probably induced by the elevated TNF-alpha level, contributes to the increased serum visfatin concentrations in women with GDM.
Diabetes research and clinical practice 10/2010; 90(1):60-5. · 2.16 Impact Factor