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.

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 Prevalence of pregnancy induced thyroid disorders, diabetes and hypertension in a tertiary care teaching hospital: an observational study

2019 ◽  
Vol 8 (8) ◽  
pp. 3201
Author(s):  
Gowthami Mummalaneni ◽  
Tamaraba Narasingarao ◽  
Krishna Kumari Myneni
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Gestational Hypertension ◽  
Tertiary Care ◽  
Thyroid Disorders ◽  
Gestational Period ◽  
South Indian ◽  
Wide Range ◽  
Study Population

Background: Pregnancy induced thyroid disorders, gestational diabetes mellitus (GDM) and gestational hypertension are common problems in women with gestational period. Published literate shows wide range of prevalence in pregnancy induced disorders in other states of India, and as of now the exact prevalence in our study population is not studied. Hence, there present study was aimed to know the prevalence of pregnancy induced disorders in pregnant women in South Indian population.Methods: A total of 120 subjects were followed-up at the time of recruitment to entire gestational period. Standard guidelines were followed for the assessment of thyroid hormone levels, glucose tolerance test (OGTT) and blood pressure values at different intervals and positions. Apart from detailed clinical history has been taken and routine basic and obstetrical investigations were done.Results: Prevalence of thyroid dysfunction (15.0%), gestational diabetes mellitus (11.7%) and gestational hypertension (9.2%) was reported in the present study population. Subclinical hypothyroidism was highest prevalence amount thyroid disorders. Gestational diabetes subjects have mean blood glucose levels of 230.68±17.48 mg/dL with OGTT test. Gestational hypertensive patients had SBP of 152.4±10.8 and DBP of 96.6±6.4; pre-hypertensive subjects had SBP of 134.2±5.48 and DBP of 6.8±4.6 respectively.Conclusions: Our study findings were slightly higher than normal prevalence’s which are reported earlier by various authors. We suggested that early screening, diagnosis and treatment are warranted for the prevention of maternal and fetal complications in Indian population. 

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 Molecular cloning and characterization of thyroid hormone receptors in teleost fish

2001 ◽  
Vol 26 (1) ◽  
pp. 51-65 ◽  
Author(s):  
O Marchand ◽  
R Safi ◽  
H Escriva ◽  
E Van Rompaey ◽  
P Prunet ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Teleost Fish ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Nuclear Hormone Receptor ◽  
Hormone Response Elements ◽  
Reverse Transcription Pcr ◽  
Wide Range

Thyroid hormones are pleiotropic factors important for many developmental and physiological functions in vertebrates. Their effects are mediated by two specific receptors (TRalpha and TRbeta) which are members of the nuclear hormone receptor superfamily. To clarify the function of these receptors, our laboratory has started a comparative study of their role in teleost fish. This type of approach has been hampered by the isolation of specific clones for each fish species studied. In this report, we describe an efficient reverse transcription/PCR procedure that allows the isolation of large fragments corresponding to TRalpha and TRbeta of a wide range of teleost fish. Phylogenetic analysis of these receptors revealed a placement consistent with their origin, sequences from teleost fish being clearly monophyletic for both TRalpha and TRbeta. Interestingly, this approach allowed us to isolate (from tilapia and salmon) several new TRalpha or TRbeta isoforms resulting from alternative splicing. These isoforms correspond to expressed transcripts and thus may have an important physiological function. In addition, we isolated a cDNA encoding TRbeta in the Atlantic salmon (Salmo salar) encoding a functional thyroid hormone receptor which binds specific thyroid hormone response elements and regulates transcription in response to thyroid hormones.

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 Survey of obstetric and neonatal outcome in gestational diabetes mellitus

2021 ◽  
Vol 10 (11) ◽  
pp. 4278
Author(s):  
J. Princy Emil Josephine ◽  
Susan William
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Tertiary Care ◽  
Challenge Test ◽  
Birth Asphyxia ◽  
Fetal Outcome ◽  
Wide Range

Background: India being the diabetic capital of the world, Indian women have a high prevalence of gestational diabetes mellitus (16.5%). It can cause a wide range of complications as well as long term implications in both the mother and fetus. A large proportion of women also progress to become overt diabetics in the future hampering with their quality of life by causing morbidity in various forms. Aim of this study is to evaluate the fetomaternal outcome in women with gestational diabetes mellitus at a tertiary care teaching hospital and the incidence of glucose intolerance in these women during the postpartum period.Methods: All patients attending the antenatal OPD were offered a 75g glucose challenge test and 200 patients diagnosed with GDM were included in the study for a period of one year. Fetomaternal complications were studied and postpartum follow up was done in these patients.Results: Out of these 200 women, 49% delivered via LSCS, 46% via labor naturalis and 5% via instrumental delivery. 59.5% were on insulin and 40.5% were treated with meal plan. Pre-eclampsia complicating pregnancy was seen in 26%, polyhydramnios was encountered in 17.5%, Urinary tract infection in 11%, preterm labour in 8.5% and PROM in 7%. Adverse fetal outcome was seen in 5% of the babies. Birth asphyxia was seen in 7.5%, macrosomia in 13%, 5% of the babies had congenital anomalies. In the postapartum follow up at 6 weeks 22.5% of the study population were glucose intolerant (75 gm OGTT).Conclusions: Early detection and prompt management of this condition can tremendously reduce the short term and long-term complications in both the mother and fetus.

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 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.

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