The Jerusalem Perinatal Study (JPS) aimed to examine the developmental origins of cardiometabolic risk.
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PROVIDER: EGAS00001004075 | EGA |
REPOSITORIES: EGA
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Project description:Perinatal nutritional imbalances may have long-lasting consequences on health and disease, increasing risk of obesity, insulin resistance, type 2 diabetes or cardiovascular disease. This idea has been conceptualized in the Developmental Origins of Health and Disease Hypothesis (DOHaD). In addition, there is evidence that such early-programmed phenotypes can be transmitted to the following generation(s). It is proposed that, environmentally induced, transmission of disease risk is mediated by epigenetic mechanisms. The aim of this study was to determine whether patterns of gene expression in the first generation offspring are also present in the following generation offspring, via the paternal lineage. Paternal transmission of patterns of gene expression strongly suggest epigenetic inheritance of disease risk. Liver tissue was obtained from the follwing experimental groups: a) control male mice, b) adult male mice previously exposed to 50% caloric restriction in utero (IUGR), c) adult male mice overfed during lactation (ON), d) adult male offspring from control mice, e) adult male offspring from IUGR mice and f) adult male offspring from ON mice.RNA was extracted and processed for further hybridization on Affymetrix microarrays (GeneChip Mouse Genome 430 2.0 (Affymetrix, Santa Clara, CA)).
2015-02-01 | E-GEOD-55304 | biostudies-arrayexpress
Project description:Background: It is well-established that cancer treatment substantially increases risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Methods: We included 2,052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA. Results: By performing multiple treatment-specific EWAS, we identified 935 5’-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 538 genes/regions associated with one or more cancer treatments at epigenome-wide significance level (P<9×10-8). Among the treatment-associated CpGs, 8 were associated with obesity, 63 with hypercholesterolemia, and 17 with hypertriglyceridemia (False-Discovery-Rate-Adjusted P<0.05). We observed substantial mediation by methylation at four independent CpGs (cg06963130, cg21922478, cg22976567, cg07403981) for association between abdominal field radiotherapy (abdominal-RT) and risk of hypercholesterolemia (70.3%) and by methylation at three CpGs (cg19634849, cg13552692, cg09853238) for association between abdominal-RT and hypertriglyceridemia (54.6%). In addition, three CpGs (cg26572901, cg12715065, cg21163477) partially mediated the association between brain-RT and obesity with 32.9% mediation effect and two CpGs mediated the association between corticosteroids and obesity (cg22351187, 14.2%) and between brain-RT and hypertriglyceridemia (cg13360224, 10.5%). Notably, several mediator CpGs reside in the proximity of well-established dyslipidemia genes: cg21922478 (ITGA1) and cg22976567 (LMNA). Conclusions: In childhood cancer survivors, cancer treatment exposures are associated with DNAm patterns present decades following the exposure. Treatment-associated DNAm sites may mediate the causal pathway from specific treatment exposures to certain cardiometabolic conditions, suggesting the utility of DNAm sites as risk predictors and potential mechanistic targets for future intervention studies.
2021-03-19 | GSE169156 | GEO
Project description:The Jerusalem Perinatal Study (JPS) aimed to examine the developmental origins of cardiometabolic risk.
| EGAD00010001816 | EGA
Project description:Maternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposures induce changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period and its effect on neuronal plasticity and cardiometabolic health in adult offspring. C57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months duration. Maternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed on HCD exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. Genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA in programmed male offspring. Methyl-seq data were supported by our findings of astrogliosis and microgliosis as well as increased microglial activation in programmed males in the paraventricular nucleus (PVN). Aligned with programming-induced protective effect in HCD male mice, we observed lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed male mice. In conclusion, our study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia. On the other hand, we observed a compensatory role of programming potentially by priming metabolic pathways to handle excess nutrients in a more efficient way.
2024-01-31 | GSE242188 | GEO
Project description:Maternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposures induce changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period and its effect on neuronal plasticity and cardiometabolic health in adult offspring. C57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months duration. Maternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed on HCD exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. Genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA in programmed male offspring. Methyl-seq data were supported by our findings of astrogliosis and microgliosis as well as increased microglial activation in programmed males in the paraventricular nucleus (PVN). Aligned with programming-induced protective effect in HCD male mice, we observed lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed male mice. In conclusion, our study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia. On the other hand, we observed a compensatory role of programming potentially by priming metabolic pathways to handle excess nutrients in a more efficient way.
2024-01-31 | GSE242187 | GEO
Project description:Maternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposures induce changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period and its effect on neuronal plasticity and cardiometabolic health in adult offspring. C57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months duration. Maternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed on HCD exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. Genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA in programmed male offspring. Methyl-seq data were supported by our findings of astrogliosis and microgliosis as well as increased microglial activation in programmed males in the paraventricular nucleus (PVN). Aligned with programming-induced protective effect in HCD male mice, we observed lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed male mice. In conclusion, our study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia. On the other hand, we observed a compensatory role of programming potentially by priming metabolic pathways to handle excess nutrients in a more efficient way.
2024-01-31 | GSE242186 | GEO
Project description:Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity
| PRJNA1021253 | ENA
Project description:Heterosis occurs where F1 offspring display superior characteristics to the parents. Heterosis is usually considered to result from crosses of genetically distinct (e.g. homozygous inbred) parents producing heterozygous F1 offspring. Most mechanistic models for heterosis require genetically heterozygous F1 hybrid offspring harbouring allelic diversity. Epigenetic or dosage models for heterosis could allow for heterosis effects in F1 offspring that display no allelic diversity with their parents. Reciprocal inter-ploidy crosses between diploid (2x) and tetraploid (4x) lines in the same genetic background generates genetically identical F1 triploids (3x). Such reciprocal F1 triploids differ according to whether the additional chromosome set is either maternally (maternal excess) or paternally inherited (paternal excess). Biomass accumulation and abiotic stress tolerance between the parental (2x and 4x) and reciprocal F1 triploid (3x) offspring of Arabidopsis thaliana accession C24 reveals a strong parental genome-dosage induced heterosis in the paternal-excess triploid F1 plants. In these F1 triploids, the circadian clock related genes CCA1 and TOC1, and the growth factors PIF4 and PIF5, display different expression levels compared to the non-heterotic maternal excess F1 triploid siblings. Whole transcriptome profiling reveals a paternal genome dosage effect on gene expression levels with strong enrichment for dysregulated abiotic stress-related genes in the paternal excess F1 triploids. This study demonstrates that heterosis can be triggered without allelic diversity in F1 triploid plants. Heterosis without heterozygosity in plants can be induced via an epigenetic “chromosome imprinting” like parental genome dosage effect requiring paternal transmission of an additional chromosome set 4 or 5 biological replicates per ploidy level, each replicate being a single two weeks old seedling
2014-08-01 | E-GEOD-52885 | biostudies-arrayexpress
Project description:Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE) and significantly contributes to morbidity and mortality. To date, no pharmacologic intervention has shown to reduce CV risk in SLE. Dysregulation of innate immune responses, including aberrant type I-Interferon (IFN)-neutrophil interactions, has been proposed to significantly contribute to enhanced CV risk in SLE. In lupus animal models, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We hypothesized that JAK/STAT inhibition in SLE subjects would result in amelioration of cardiometabolic and immunologic parameters previously associated with enhanced CVD risk.
2021-03-01 | GSE139940 | GEO
Project description:Parental exposure to environmental stress can result in an increased diseases risk in the offspring. Although literature on maternal contribution to hereditary diseases are growing, the paternal contribution is frequently underrecognized. Since human studies reported that 80% of transmitted mutations arise in the paternal germline, it is crucial to understand the mechanism underlying the paternally inherited genome instability. Ionizing radiation (IR) is a major source of mutagenesis through inducing DNA double-strand breaks (DSBs). Here, we used sex-separated C. elegans mutants to investigate the paternal contribution to IR-induced transgenerational effects. Specifically, we found that paternal exposure to IR leads to a transgenerational embryonic lethality, and this effect is only observed when the radiation exposure occurred close to the time of fertilization. In the offspring of the irradiated males (F1 generation), we detected various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement, and aneuploidy. These phenotypes are attributed to the usage of two error-prone repair machinery, the polymerase-theta mediated end joining (TMEJ) and the non-homologous End Joining (NHEJ). Surprisingly, depletion of a human histone H1.0 ortholog, HIS-24, can significantly rescue this transgenerational embryonic lethality. Moreover, this rescue effect is associated with the downregulation of heterochromatin marker histone 3 lysine 9 di-methylation (H3K9me2), and the knocking-down of heterochromatin protein, HPL-1, could mimic the rescue effect of HIS-24 depletion. We also noticed that removal of the histone H1 and heterochromatin marker could activate the error-free repair machinery, Homologous Recombination repair (HR), thus improving the viability of the offspring carrying paternally inherited DNA damage. Altogether, our work sheds light on the importance of paternal radiation exposure on the health of offspring. In addition, our work establishes a previously unknown mechanism underlying the transgenerational genome instability and provides a potential therapeutic target for preventing the hereditary diseases caused by paternal radiation exposure.
2022-10-18 | PXD031873 | Pride