Maternal High Fat Diet and Diabetes Disrupts Transcriptomic Pathways that Regulate Cardiac Metabolism and Cell Fate in Newborn Rat Hearts
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PROVIDER: PRJNA633098 | ENA |
REPOSITORIES: ENA
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Project description:Children born to diabetic and obese or overweight mothers have a higher risk of heart disease at birth and later in life. Our previous work using chromatin immunoprecipitation sequencing revealed that late-gestation diabetes in combination with maternal high fat diet causes a distinct fuel-mediated epigenetic reprogramming of cardiac tissue during fetal cardiogenesis. We used gene expression profiling to investigate the overall transcriptional signature of newborn rat offspring exposed to the combination of maternal diabetes and maternal high fat diet.
2020-09-02 | GSE150649 | GEO
Project description:Background: Children born to diabetic or obese mothers have a higher risk of heart disease at birth and later in life. Using chromatin immunoprecipitation sequencing, we previously demonstrated that late-gestation diabetes, maternal high fat (HF) diet, and the combination causes distinct fuel-mediated epigenetic reprogramming of rat cardiac tissue during fetal cardiogenesis. The objective of the present study was to investigate the overall transcriptional signature of newborn offspring exposed to maternal diabetes and maternal H diet. Methods: Microarray gene expression profiling of hearts from diabetes exposed, HF diet exposed, and combination exposed newborn rats was compared to controls. Functional annotation, pathway and network analysis of differentially expressed genes were performed in combination exposed and control newborn rat hearts. Further downstream metabolic assessments included measurement of total and phosphorylated AKT2 and GSK3β, as well as quantification of glycolytic capacity by extracellular flux analysis and glycogen staining. Results: Transcriptional analysis identified significant fuel-mediated changes in offspring cardiac gene expression. Specifically, functional pathways analysis identified two key signaling cascades that were functionally prioritized in combination exposed offspring hearts: (1) downregulation of fibroblast growth factor (FGF) activated PI3K/AKT pathway and (2) upregulation of peroxisome proliferator-activated receptor gamma coactivator alpha (PGC1α) mitochondrial biogenesis signaling. Functional metabolic and histochemical assays supported these transcriptome changes, corroborating diabetes- and diet-induced cardiac transcriptome remodeling and cardiac metabolism in offspring. Conclusion: This study provides the first data accounting for the compounding effects of maternal hyperglycemia and hyperlipidemia on the developmental cardiac transcriptome, and elucidates nuanced and novel features of maternal diabetes and diet on regulation of heart health.
| S-EPMC7527411 | biostudies-literature
Project description:Cardiac tissue from newborn hearts from animals exposed to excess maternal cortisol in late gestation and untreated was compared via MS lipidomic analysis
2018-11-30 | ST001106 | MetabolomicsWorkbench
Project description:Background: Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements. Results: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels. Conclusions: These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life. 168 newborn umbilical cord buffy coat samples run singly as a cross-sectional study, not case-control.
2011-08-31 | E-GEOD-27317 | biostudies-arrayexpress
Project description:Cardiac tissue from newborn hearts from animals exposed to excess maternal cortisol in late gestation and untreated was compared via NMR metabolomic analysis
2018-12-04 | ST001107 | MetabolomicsWorkbench
Project description:The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury but lose it after a week of life, which has been utilized as a valuable model to explore the cues for heart regeneration. More and more researches indicated that glycoprotein played an important role in cardiac regeneration. Elucidating the glycosylation processes associated with heart regeneration will be beneficial for the molecular mechanism studies of heart regeneration as well as discovery of potential therapeutic strategies for human cardiac diseases. In this work, an integrated glycoproteomic and proteomic analysis were performed to investigate the differences in glycoprotein abundances and site-specific glycosylation occupancy between neonatal day 1 (P1) and day 7 (P7) of mouse hearts. The intact glycoepeptides were enriched and identified in both P1 and P7 hearts. To screen for differentially regulated glycoproteins, we compared the expression levels of intact glycopeptides between P1 and P7 hearts using label free quantification. Eventually, the glycosylation occupancy of site-specific N-glycans were obtained by comparing the alterations of intact glycopeptides with their corresponding protein expression levels obtained from global proteomic analysis. These altered glycosylation patterns among proteins between P1 and P7 mouse hearts have a significant potential to aid our understanding of the regenerative capacity loss in neonatal mouse hearts during the first week, thus leading to novel therapeutic approaches to recover the capacity.
2020-05-26 | PXD017139 | Pride
Project description:Transcriptomic analysis of lungs from newborn rats born to vitamin D adequate and vitamin D deficient mothers Vitamin D deficiency during pregnancy is common and is related to several maternal and fetal morbidities. Past studies suggest that vitamin D plays a role in normal lung development and we have shown that vitamin D regulates lung alveolar and vascular growth and preserves lung structure in experimental bronchopulmonary dysplasia (BPD) through improved pro-angiogeneic signaling. In addition, maternal vitamin D deficiency causes abnormal airway, alveolar, and vascular growth, as well as impaired lung function and airway hyper-reactivity in newborn rats. However, the mechanisms responsible for these physiologic effects are unknown. To gain insight into the role that maternal vitamin D status has on fetal lung development we used an unbiased transcriptomic approach to identify pathways altered in the lungs of offspring from vitamin D deficient dams.
2020-09-01 | GSE136736 | GEO
Project description:ObjectiveIncreased infant birth weight and adiposity are associated with an altered risk of adult chronic diseases. The objective was to investigate the association between maternal dietary fat intake during pregnancy and newborn adiposity.Study designThe study included 79 singleton pregnancies. Associations between maternal dietary fat intake during each trimester and infant adiposity at birth were assessed.ResultAverage total grams of maternal total dietary fat and unsaturated fat intake during pregnancy correlated with infant percent body fat after adjusting for potential confounding variables (r = 0.23, p = 0.045; r = 0.24, p = 0.037). Maternal average daily intake of total fat, saturated fat, and unsaturated fat during the second trimester of pregnancy were each associated with infant percent body fat (r = 0.25, p = 0.029; r = 0.23, p = 0.046; r = 0.25, p = 0.031; respectively).ConclusionsThe second trimester of pregnancy is a key time period for fetal adipose tissue metabolic programming and therefore a target for nutritional intervention.
| S-EPMC8119319 | biostudies-literature
Project description:We conducted a genome-wide placental transcriptome study aiming at the identification of functional pathways representing the molecular link between maternal pre-pregnancy BMI and fetal growth. We used RNA microarray (Agilent 8 X 60 K), medical records, and questionnaire data from 183 mother-newborn pairs from the ENVIRONAGE birth cohort study (Flanders, Belgium). We applied a weighted gene co-expression network analysis (WGCNA) and identified genes modules and hub genes that were associated with maternal BMI as well as newborn birth weight. Modules of interest were further characterized by gene ontology (GO) and pathway enrichment analyses. We assessed the mediating effects of modules and hub genes in the association between maternal BMI and newborn weight.
2019-03-16 | GSE128381 | GEO