Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1045863 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26965108.fastq.gz | Fastqsanger.gz | |||
| SRR26965109.fastq.gz | Fastqsanger.gz | |||
| SRR26965110.fastq.gz | Fastqsanger.gz | |||
| SRR26965111.fastq.gz | Fastqsanger.gz | |||
| SRR26965112.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 5 |
Similar Datasets
Project description:Maternal diabetes is a recognized risk factor for both short-term and long-term complications in offspring. Beyond the direct teratogenicity of maternal diabetes, the intrauterine environment can influence offspring cardiovascular health. Abnormalities in the cardiac sympathetic system are implicated in conditions such as sudden infant death syndrome, cardiac arrhythmic death, heart failure, and certain congenital heart defects in children from diabetic pregnancies. However, the mechanisms by which maternal diabetes affect the development of the cardiac sympathetic system and consequently, heightening health risks and predisposing to cardiovascular disease remain poorly understood. In this study, we present a comprehensive analysis of the combined impact of a Hif1a-deficient sympathetic system and the maternal diabetes environment on both heart development and the formation of the cardiac sympathetic system. The synergic negative effect of exposure to maternal diabetes and Hif1a deficiency resulted in the most pronounced deficit in cardiac sympathetic innervation and the development of adrenal medulla. Abnormalities in the cardiac sympathetic system were accompanied by a smaller heart, reduced ventricular wall thickness, dilated subepicardial veins, and coronary arteries in the myocardium, along with anomalies in the branching and connections of the main coronary arteries. Transcriptional profiling by RNA-seq revealed significant transcriptome changes in Hif1a-deficient sympathetic neurons, primarily associated with cell cycle regulation, proliferation, and mitosis, explaining the shrinkage of the sympathetic neuron population. Our data demonstrate that a failure to adequately activate HIF-1α regulatory pathway, particularly in the context of maternal diabetes, may contribute to abnormalities in the cardiac sympathetic system. In conclusion, our findings indicate that the interplay between deficiencies in the cardiac sympathetic system and subtle structural alternations in the vasculature, microvasculature, and myocardium during heart development not only increases the risk of cardiovascular disease but also diminishes the adaptability to the stress associated with the transition to extrauterine life, thus, increasing the risk of neonatal death.
2024-02-29 | GSE250606 | GEO
Project description:We analysed the combined effects of exposure to maternal diabetes and disrupted HIF-1 signaling on the transcriptom in cardiac left ventricles of 12 weeks old male mice. This approach provides the information about the long term changes originating in utero due to maternal diabetes and inefficient response to hypoxia which develops as a result of hyperglycemia. The majority of changes were detected in Hif1a insufficient mice exposed to maternal diabetes.
2018-05-15 | GSE109633 | GEO
Project description:Maternal diabetes during early pregnancy can cause birth defects, notably of the developing heart and nervous system. To recognize the gene expression differences that may be the basis for such birth defects, we performed RNA-Seq on mouse embryos of the Non-Obese Diabetic (NOD) strain. Mice of that strain spontaneously develop type I diabetes.
2022-05-04 | GSE197396 | GEO
Project description:Effects of Hif1a mutation and maternal diabetes on the offspring heart
| PRJNA431568 | ENA
Project description:Maternal diabetes causes cardiac malformations in fetuses. In this study, we have analyzed the differential gene expression profiling in the developing heart of embryos from diabetic and control mice by using the oligonucleotide microarray. Expression patterns of genes and proteins that are differentially expressed in the developing heart were further examined by the real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Embryos of diabetic pregnancies displayed cardiac malformations. Microarray analysis revealed the genes that were altered in expression level in the developing heart of embryos from diabetic mice when compared to controls. It is concluded that altered expression of a variety of genes involved in heart development is associated with cardiac malformations in offsprings of diabetic mother. We used microarrays to identify the genes specific to the developing heart of embryos from control and diabetic mice RNA was isolated from heart tissue of control and diabetes exposed E13.5 and E15.5 mouse embryos (three samples each). The RNA was hybridised onto Affymetrix Mouse Genome 430 2.0 Array.
2011-09-13 | E-GEOD-32078 | biostudies-arrayexpress
Project description:Congenital heart disease (CHD) is the most prevalent structural malformations of the heart affecting ∼1% of live births. To date, both damaging genetic variations and adverse environmental exposure such as maternal diabetes have been found to cause CHD. Clinical studies show ∼fivefold higher risk of CHD in the offspring of mothers with pregestational diabetes. Maternal pregestational diabetes affects the gene regulatory networks key to proper cardiac development in the fetus. However, the cell-type specificity of these gene regulatory responses to maternal diabetes and their association with the observed cardiac defects in the fetuses remains unknown. To uncover the transcriptional responses to maternal diabetes in the early embryonic heart, we used an established murine model of pregestational diabetes. In this model, we have previously demonstrated an increased incidence of CHD. Here, we show maternal hyperglycemia (matHG) elicits diverse cellular responses during heart development by single-cell RNA-sequencing in embryonic hearts exposed to control and matHG environment. Through differential gene-expression and pseudotime trajectory analyses of this data, we identified changes in lineage specifying transcription factors, predominantly affecting Isl1+ second heart field progenitors and Tnnt2+cardiomyocytes with matHG. Using in vivo cell-lineage tracing studies, we confirmed that matHG exposure leads to impaired second heart field-derived cardiomyocyte differentiation. Finally, this work identifies matHG-mediated transcriptional determinants in cardiac cell lineages elevate CHD risk and show perturbations in Isl1-dependent gene-regulatory network (Isl1-GRN) affect cardiomyocyte differentiation. Functional analysis of this GRN in cardiac progenitor cells will provide further mechanistic insights into matHG-induced severity of CHD associated with diabetic pregnancies.
2022-07-22 | GSE193746 | GEO
Project description:Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs. We compared E10.5 cntrol embryos to E10.5 embryos from diabetic pregnancies in the FVB mouse strain.
2012-09-25 | GSE41095 | GEO
Project description:The prevalence of diabetes has significantly increased among women of childbearing age worldwide, and it is known that infants who are exposed to maternal diabetes in utero are at increased risk of congenital anomalies of the kidney and urinary tract. The primary role of the kidney is to filter blood through the nephrons. These anomalies can result in a reduction in the number of nephrons that are formed during kidney development, or decreased congenital nephron endowment, which is linked to hypertension and chronic kidney disease. It is unknown how exposure to maternal diabetes in utero results in abnormal kidney development and the long-term health consequences of this exposure remain ill-defined. In this study, we profiled gene expression in the developing mouse kidney from C57BL/6J control and maternal diabetes exposed (DM_Exp) mice at single cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney.
2024-11-01 | GSE162298 | GEO
Project description:Congenital heart defects (CHD) are one of the most common defects in offspring of diabetic mothers. There is a clear association between maternal diabetes and CHD; however the underlying molecular mechanism remains unknown. We hypothesized that maternal diabetes affects with the expression of early developmental genes that regulate the essential developmental processes of the heart, thereby resulting in the pathogenesis of CHD. We analyzed genome-wide expression profiling in the developing heart of embryos from diabetic and control mice by using the oligonucleotide microarray. Microarray analysis revealed that a total of 878 genes exhibited more than 1.5 fold changes in expression level in the hearts of experimental embryos in either E13.5 or E15.5 compared with their respective controls. Expression pattern of genes that is differentially expressed in the developing heart was further examined by the real-time reverse transcriptase-polymerase chain reaction. Several genes involved in a number of molecular signaling pathways such as apoptosis, proliferation, migration and differentiation in the developing heart were differentially expressed in embryos of diabetic pregnancy. It is concluded that altered expression of several genes involved in heart development may contribute to CHD in offspring of diabetic mothers.
2011-09-14 | GSE32078 | GEO
Project description:Diabetic embryopathy can affect any developing organ system, although cardiovascular malformations, neural tube defects and caudal dysgenesis syndrome are the most prominent congenital malformations. We hypothesize that the metabolic imbalance occurring in diabetic pregnancy de-regulates tissue specific gene expression programs in the developing embryo. In order to identify genes whose expression is affected by maternal diabetes, we analyzed gene expression profiles of diabetes-exposed mouse embryos by using Affymetrix microarrays. We identified 129 genes with altered expression levels; 21 genes had increased and 108 genes had decreased expression levels in diabetes-exposed embryos relative to controls. A substantial fraction of these genes (35) are essential for normal embryonic development as shown by functional studies in mouse models. The largest fraction of diabetes-affected genes was in transcription factor and DNA-binding/chromatin remodeling functional categories (19%), which directly affect transcription. These findings suggest that transcriptional regulation in the developing embryos is perturbed by maternal diabetes and that transcriptional regulation plays a major role in the responses of embryos to intrauterine exposure to diabetic conditions. Interestingly, we found the expression of hypoxia-inducible factor 1 α (Hif1α) deregulated in the embryos exposed to the conditions of maternal diabetes. Since hypoxic stress is associated with the complications of diabetic pregnancy, we performed a post-hoc analysis of our microarray data with a specific focus on known HIF1 target genes. Of 39 genes detected in our microarrays, the expression changes of 22 genes (20 were increased and two genes were decreased in diabetes-exposed embryos) were statistically significant. These results indicate that HIF1-regulated pathways are affected in diabetes-exposed embryos. These results strongly suggest that de-regulation of hypoxia/HIF1 activated pathways could be the one of the key molecular events associated with the exposure to the teratogenic intrauterine environment of a diabetic mother. Keywords: Comparative studies of embryonic response to maternal diabetes
2009-07-21 | GSE9675 | GEO