scholarly journals Analysis of key genes and their functions in placental tissue of patients with gestational diabetes mellitus

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Yuxia Wang ◽  
Haifeng Yu ◽  
Fangmei Liu ◽  
Xiue Song
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Tyrosine Phosphatase ◽  
Human Leukocyte ◽  
Placental Tissue ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Tissue Samples ◽  
Key Genes

Abstract Background This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM). Methods The GSE70493 dataset used for this study was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in the placental tissue of women with GDM in relation to the control tissue samples were identified and submitted to protein-protein interaction (PPI) network analysis and subnetwork module mining. Functional enrichment analyses of the PPI network and subnetworks were subsequently carried out. Finally, the integrated miRNA–transcription factor (TF)–DEG regulatory network was analyzed. Results In total, 238 DEGs were identified, of which 162 were upregulated and 76 were downregulated. Through PPI network construction, 108 nodes and 278 gene pairs were obtained, from which chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, protein tyrosine phosphatase, receptor type C (PTPRC), and human leukocyte antigen (HLA) were screened out as hub genes. Moreover, genes associated with the immune-related pathway and immune responses were found to be significantly enriched in the process of GDM. Finally, miRNAs and TFs that target the DEGs were predicted. Conclusions Four candidate genes (viz., CXCL9, CXCL10, PTPRC, and HLA) are closely related to GDM. miR-223-3p, miR-520, and thioredoxin-binding protein may play important roles in the pathogenesis of this disease.

Elevated pro-angiogenic phenotype in feto-placental tissue from gestational diabetes mellitus

Placenta ◽  
2015 ◽  
Vol 36 (4) ◽  
pp. 485
Author(s):  
F. Troncoso ◽  
J. Acurio ◽  
K. Herlitz ◽  
F. Ruiz ◽  
P. Bertoglia ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Placental Tissue

scholarly journals Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus

2009 ◽  
Vol 160 (4) ◽  
pp. 567-578 ◽  
Author(s):  
Michelle Colomiere ◽  
Michael Permezel ◽  
Clyde Riley ◽  
Gernot Desoye ◽  
Martha Lappas
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Placental Tissue ◽  
Insulin Signaling Pathway ◽  
Obese Patients ◽  
Obese Women ◽  
Normal Controls

ObjectiveStudies in adipose tissue and skeletal muscle suggest that impaired insulin action is due to defects in the insulin signaling pathway and may play a role in the pathophysiology of insulin resistance associated with gestational diabetes mellitus (GDM) and obesity. The present study tested the hypothesis that endogenous expression levels in the human term placenta of insulin signaling components are altered in placental tissue from GDM women in comparison with normal controls and maternal obesity.Design and methodsPlacental tissue was collected from normal, diet-controlled GDM, and insulin-controlled GDM in both non-obese and obese women (n=6–7 per group). Western blotting and quantitative RT-PCR was performed to determine the level of expression in the insulin signaling pathway.ResultsThere was a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein expression in non-obese women with insulin-controlled GDM compared with diet-controlled GDM and normal controls. Furthermore, a decrease in both protein and mRNA expression of phosphatidyl-inositol-3-kinase (PI3-K) p85α and glucose transporter (GLUT)-4 was observed in non-obese and obese women with insulin controlled GDM compared with normal controls. When comparing non-obese to obese patients, significant decreases in mRNA expression of IR-β, PI3K p85α and GLUT-4 was found in obese patients.ConclusionOur results suggest that post receptor defects are present in the insulin signaling pathway in placenta of women with pregnancies complicated by diabetes and obesity. In addition, expression studies demonstrate post receptor alterations in insulin signaling possibly under selective maternal regulation and not fetal regulation.

scholarly journals Cell Type- and Sex-Specific Dysregulation of Thyroid Hormone Receptors in Placentas in Gestational Diabetes Mellitus

2020 ◽  
Vol 21 (11) ◽  
pp. 4056 ◽  
Author(s):  
Julia Knabl ◽  
Lena de Maiziere ◽  
Rebecca Hüttenbrenner ◽  
Stefan Hutter ◽  
Julia Jückstock ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Thyroid Hormone ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Placental Tissue ◽  
Cell Type ◽  
Decidual Cells ◽  
Wide Range

Thyroid hormones are essential for development of trophoblasts and the fetus. They also regulate a wide range of metabolic processes. We investigated the influence of maternal gestational diabetes mellitus (GDM) on thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRβ1 and THRβ2 of the human placenta in a sex- and cell-type specific manner. Term placental tissue was obtained from women with (n = 40) or without GDM (control; n = 40). THRs levels were measured by semi-quantitative immunohistochemistry and real-time qRT-PCR. We localized THR immunostaining in syncytiotrophoblast (SCT), which was the tissue with the strongest signal. Double immunofluorescence identified THR in decidual cells in the stroma and in extravillous cytotrophoblasts. GDM did not change THRα1 immunolabelling intensity in decidua, but was associated with a stronger immunolabelling in SCT compared to GDM (p < 0.05). The SCT difference of GDM vs. control was strongest (p < 0.01) in female placentas. THRα2 was only weakly present and immunolabelling was weaker (p < 0.05) in SCT of only male GDM placentas in comparison to male controls. THRβ1/β2 immunostaining was weak in all cell types without changes in GDM. However, more THRβ1/2 protein was present (p < 0.001) in male than female placentas. All these protein changes were paralleled by changes of THR transcript levels. The data show that THR are expressed in term trophoblast in relation to fetal sex. Maternal GDM influences predominantly THRα1 in SCT, with the strongest GDM effect in SCT of female placentas.

scholarly journals Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus

Epigenomics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1371-1385 ◽  
Author(s):  
Angela Steyn ◽  
Nigel J Crowther ◽  
Shane A Norris ◽  
Raquel Rabionet ◽  
Xavier Estivill ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Epigenetic Modification ◽  
Placental Tissue ◽  
Maternal Blood ◽  
Pentose Phosphate ◽  
Igf Binding Proteins ◽  
Genes Encoding ◽  
Igf Binding

Aim: Gestational diabetes mellitus (GDM) has been linked with adverse long-term health outcomes for the fetus and mother. These effects may be mediated by epigenetic modifications. Materials & methods: Genome-wide RNA sequencing was performed in placental tissue and maternal blood in six GDM and six non-GDM pregnancies. Promoter region DNA methylation was examined for selected genes and correlated with gene expression to examine an epigenetic modulator mechanism. Results: Reductions of mRNA expression and increases in promoter methylation were observed for G6PD in GDM women, and for genes encoding IGF-binding proteins in GDM-exposed placenta. Conclusion: GDM involves epigenetic attenuation of G6PD, which may lead to hyperglycemia and oxidative stress, and the IGF-axis, which may modulate fetal macrosomia.

scholarly journals Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Francisco Visiedo ◽  
Celeste Santos-Rosendo ◽  
Rosa M. Mateos-Bernal ◽  
M. del Mar Gil-Sánchez ◽  
Fernando Bugatto ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Protein Modification ◽  
Placental Tissue ◽  
No Production ◽  
Protein Activity ◽  
Cellular Signal ◽  
Posttranslational Protein Modification ◽  
Biotin Switch

Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n=8) and GDM (n=8) pregnancies. S-Nitrosylation was measured using the biotin-switch assay, while the expression and protein activity were assessed by immunoblotting and colorimetric methods, respectively. Results indicated that catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas, and that was accompanied by reduced catalase activity. S-Nitrosylation of ERK1/2 and AKT was increased in GDM placentas, and their activities were inhibited. Activities of caspase-3 and caspase-9 were increased, with the latter also showing diminished nitrosylation levels. These findings suggest that S-nitrosylation is a little-known, but critical, mechanism by which NO directly modulates key placental proteins in women with GDM and, as a consequence, maternal and fetal anomalies during pregnancy can occur.

scholarly journals Identification of Diagnostic CpG Signatures in Patients with Gestational Diabetes Mellitus via Epigenome-Wide Association Study Integrated with Machine Learning

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yan Liu ◽  
Hui Geng ◽  
Bide Duan ◽  
Xiuzhi Yang ◽  
Airong Ma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Machine Learning ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Association Study ◽  
Cpg Methylation ◽  
Ppi Network ◽  
Cpg Sites ◽  
Model Based ◽  
Svm Model

Background. Gestational diabetes mellitus (GDM) is the most prevalent metabolic disease during pregnancy, but the diagnosis is controversial and lagging partly due to the lack of useful biomarkers. CpG methylation is involved in the development of GDM. However, the specific CpG methylation sites serving as diagnostic biomarkers of GDM remain unclear. Here, we aimed to explore CpG signatures and establish the predicting model for the GDM diagnosis. Methods. DNA methylation data of GSE88929 and GSE102177 were obtained from the GEO database, followed by the epigenome-wide association study (EWAS). GO and KEGG pathway analyses were performed by using the clusterProfiler package of R. The PPI network was constructed in the STRING database and Cytoscape software. The SVM model was established, in which the β-values of selected CpG sites were the predictor variable and the occurrence of GDM was the outcome variable. Results. We identified 62 significant CpG methylation sites in the GDM samples compared with the control samples. GO and KEGG analyses based on the 62 CpG sites demonstrated that several essential cellular processes and signaling pathways were enriched in the system. A total of 12 hub genes related to the identified CpG sites were found in the PPI network. The SVM model based on the selected CpGs within the promoter region, including cg00922748, cg05216211, cg05376185, cg06617468, cg17097119, and cg22385669, was established, and the AUC values of the training set and testing set in the model were 0.8138 and 0.7576. The AUC value of the independent validation set of GSE102177 was 0.6667. Conclusion. We identified potential diagnostic CpG signatures by EWAS integrated with the SVM model. The SVM model based on the identified 6 CpG sites reliably predicted the GDM occurrence, contributing to the diagnosis of GDM. Our finding provides new insights into the cross-application of EWAS and machine learning in GDM investigation.

scholarly journals Soluble human leukocyte antigen-G evaluation in pregnant women with gestational diabetes mellitus

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Muhamad R. Abdel Hameed ◽  
Osama Ahmed Ibrahiem ◽  
Entsar Hamed Ahmed ◽  
Paula Rofaeel Sedky ◽  
Naglaa Mohamed M. A. Mousa
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Human Leukocyte Antigen ◽  
Pregnant Women ◽  
Human Leukocyte ◽  
Normal Pregnancy ◽  
Human Major Histocompatibility Complex ◽  
Leukocyte Antigen ◽  
Soluble Hla

Abstract Background Gestational diabetes mellitus is any degree of glucose intolerance with onset or first recognition occurring late in second trimester and third trimester of pregnancy. It constitutes a greater impact on diabetes epidemic as it carries a major risk for developing type 2 diabetes mellitus to the mother and her fetus later in life. human leukocyte antigen (HLA)-G is a class Ib gene presents in the human major histocompatibility complex (MHC). HLA-G has an important role for mother and fetus tolerance during pregnancy, also in the pancreatic islet cells protection. This is a case-control study, measuring serum HLA-G levels by ELISA in 60 pregnant women with gestational diabetes compared with 36 normal pregnant women. Results HLA-G levels were significantly high in pregnant women with gestational diabetes mellitus (GDM) in contrast to women with normal pregnancy (P = 0.001). Conclusion Women with GDM had significantly higher levels of soluble HLA-G than women without GDM, suggesting that HLA-G molecule is among the factors for regulation and control of the immune response and the induction of tolerance. Soluble HLA-G could be considered an important follow-up investigation for all pregnant primary health care for early detection of gestational diabetes.

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