Effects of Hif1a mutation and maternal diabetes on the offspring heart
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431568 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6511410_1.fastq.gz | Fastqsanger.gz | |||
| SRR6511410_2.fastq.gz | Fastqsanger.gz | |||
| SRR6511411_1.fastq.gz | Fastqsanger.gz | |||
| SRR6511411_2.fastq.gz | Fastqsanger.gz | |||
| SRR6511412_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
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 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:BACKGROUND:Epidemiological studies show that maternal diabetes predisposes offspring to cardiovascular and metabolic disorders. However, the precise mechanisms for the underlying penetrance and disease predisposition remain poorly understood. We examined whether hypoxia-inducible factor 1 alpha, in combination with exposure to a diabetic intrauterine environment, influences the function and molecular structure of the adult offspring heart. METHODS AND RESULTS:In a mouse model, we demonstrated that haploinsufficient (Hif1a+/-) offspring from a diabetic pregnancy developed left ventricle dysfunction at 12 weeks of age, as manifested by decreased fractional shortening and structural remodeling of the myocardium. Transcriptional profiling by RNA-seq revealed significant transcriptome changes in the left ventricle of diabetes-exposed Hif1a+/- offspring associated with development, metabolism, apoptosis, and blood vessel physiology. In contrast, both wild type and Hif1a+/- offspring from diabetic pregnancies showed changes in immune system processes and inflammatory responses. Immunohistochemical analyses demonstrated that the combination of haploinsufficiency of Hif1a and exposure to maternal diabetes resulted in impaired macrophage infiltration, increased levels of advanced glycation end products, and changes in vascular homeostasis in the adult offspring heart. CONCLUSIONS:Together our findings provide evidence that a global reduction in Hif1a gene dosage increases predisposition of the offspring exposed to maternal diabetes to cardiac dysfunction, and also underscore Hif1a as a critical factor in the fetal programming of adult cardiovascular disease.
| S-EPMC5948854 | biostudies-literature
Project description:Maternal obesity and diabetes is associated with increased risk of obesity and diabetes in offspring. We generated a model of maternal caloric excess in Drosophila and noted altered body composition in offspring from females fed a high-sucrose diet. To gain insight into the mechanisms underlying this response, we profiled gene expression in mid-third instar larvae (mid-L3) offspring from either control or high-sucrose fed females. All offspring were raised on control food. We used microarrays to detail the response of Drosophila larvae to maternal high calorie diet
2011-11-30 | GSE33989 | GEO
Project description:Maternal obesity and diabetes is associated with increased risk of obesity and diabetes in offspring. We generated a model of maternal caloric excess in Drosophila and noted altered body composition in offspring from females fed a high-sucrose diet. To gain insight into the mechanisms underlying this response, we profiled gene expression in mid-third instar larvae (mid-L3) offspring from either control or high-sucrose fed females. All offspring were raised on control food. We used microarrays to detail the response of Drosophila larvae to maternal high calorie diet Virgin female w1118 flies were fed control (0.15M) or high (1M) sucrose food for 7 days, mated with male w1118 flies such that all embryos were laid on control food. Mid-L3 larvae were selected for RNA extraction and hybridization on Affymetrix microarrays. Mid-L3 were selected as L2, aged overnight until early L3, then transferred to fresh control food for 12 more hours before selection.
2011-11-30 | E-GEOD-33989 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE40471: Maternal slimming reprograms metabolic gene expression in mice offspring (NimbleGen expression) GSE40477: Maternal slimming reprograms metabolic gene expression in mice offspring (NimbleGen methylation) GSE40478: Maternal slimming reprograms metabolic gene expression in mice offspring (mRNA-Seq) Refer to individual Series
2012-08-30 | E-GEOD-40479 | biostudies-arrayexpress
Project description:Evaluate differences in gene methylation levels between offspring born after maternal bariatric surgery and their siblings born before surgery Offspring born after maternal bariatric surgery (AMS, N=25) vs. offspring born before maternal surgery (BMS, N=25)
2013-05-16 | E-GEOD-44798 | biostudies-arrayexpress
Project description:Evaluate differences in gene expression levels between offspring born after maternal bariatric surgery and their siblings born before surgery Offspring born after maternal bariatric surgery (AMS, N=23) vs. offspring born before maternal surgery (BMS, N=23)
2013-05-16 | E-GEOD-44407 | biostudies-arrayexpress
Project description:Maternal high-fat consumption has negative effects on the offspring’s obesity/diabetes susceptibility and we hypothesize that epigenetic modifications in the skeletal muscle are partly responsible for this phenotype. To detect genes affected by maternal nutrition, offspring of low-fat (LF) and high-fat (HF) diet fed dams (C57BL/6 mice) received LF diet upon weaning and were sacrificed at an age of 6 or 25 weeks. M. quadriceps gene expression was investigated by microarray analysis revealing upregulation of the nuclear receptor Nr4a1 by maternal HF feeding. This was accompanied by promoter hypomethylation of CpG‑1408 which correlated with higher Nr4a1 gene expression at both ages. Offspring voluntary exercise training normalized Nr4a1 methylation/expression and ameliorated the negative effects of maternal HF feeding on insulin sensitivity. Overall, Nr4a1 expression correlated with higher insulin levels during oral glucose tolerance test and could, therefore, be involved in the programming offspring’s diabetes susceptibility.
2018-07-09 | GSE104029 | GEO
Project description:Slimming is globally prevalent especially in young women, and it may contribute to the metabolic health of their offspring. Whereas some Lamarckian ideas about environmental inheritance have been dismissed, increasing evidence suggest that certain acquired traits can be transmitted to the next generation. It is therefore of great interest to determine how and to what extent a maternal lifestyle change contributes to their offspring. Here we show that enriched environment (EE) induced maternal slimming improves general health and reprograms metabolic gene expression in mice offspring. EE in mothers induced decreased body weight, adiposity, and improved glucose tolerance and insulin sensitivity. Relative to controls, their offspring exhibited improved general health such as reduced fat accumulation, enhanced metabolic parameters as well as glucose tolerance and insulin sensitivity. Maternal slimming altered the expression of 1,732 genes in the liver of offspring, with coherent downregulation of genes involved in lipid and cholesterol biosynthesis. Epigenomic profiling in offspring revealed numerous changes in cytosine methylation depending on maternal slimming, including hypermethylation of several genes involved in lipid biosynthesis, correlated with the downregulation of these genes. Maternal slimming also altered overall transcriptome patterns in mature oocytes, which contributes largely to the metabolic health and gene expression patterns in offspring. Overall, our studies suggest that maternal slimming have a beneficial role in regulating metabolic profiles in offspring, implying that it might be considered as a potential strategy to reverse the global prevalence of obesity and related metabolic syndromes. Examination of the effect of 2 different maternal lifestyles, control and slimming, on the mRNA expression in the mature oocytes of the female mice. Naturally ovulated mature oocytes (MII stage) were collected from 3 control and 3 slimming female F0 founders (3 oocytes per mouse, 9 oocytes for each group).
2012-08-30 | E-GEOD-40478 | biostudies-arrayexpress