Epigenomic profiling in fetal brain after prenatal stress
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205087 | GEO | 2023/03/01
REPOSITORIES: GEO
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Project description:Maternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. How the effects of maternal social stress are transmitted to the developing foetus is unclear. Using a rat model of maternal social stress during pregnancy, we explored the mechanisms by which maternal stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress induced oxidative stress in the placenta, but not in the foetal brain, which was prevented by a single administration of nanoparticle-bound antioxidant prior to the stress exposure. Moreover, this antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in juvenile male offspring, along with neurological and gene expression changes in the offspring brain. In vitro, placental conditioned medium or foetal plasma from stressed pregnancies caused changes to cultured cortical neurons, similar to those observed in the brains of juvenile offspring exposed to prenatal stress, and were found to contain altered levels of extracellular microRNAs but not corticosterone. The present study highlights the crucial role of the placenta, and molecules secreted from the placenta, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.
2024-04-22 | GSE131040 | GEO
Project description:Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.
2023-11-04 | GSE246534 | GEO
Project description:Maternal stress during pregnancy exerts long-term effects on the mental well-being of the offspring. However, the long-term effect of prenatal exposure on the offspring’s mental status is only partially understood. The placenta plays a vital role in connecting the maternal side to the fetus, thereby serving as an important interface between maternal exposure and fetal development. Here, we profiled the placental transcriptome of women who were pregnant during a hurricane (Superstorm Sandy), which struck New York City in 2012. The offspring were followed longitudinally and their temperament was assessed during the first 6-12 months of age. The data identified a significant correlation between a Superstorm Sandy stress factor score and infant temperament. Further, analysis of the placental transcriptomes identified an enrichment of functional pathways related to inflammation, extracellular matrix integrity and sensory perception in the specimen from those infants with “Slow-to-Warm-up” temperament during the first year of life. Together, these findings provide initial evidence that maternal exposure to climate-related disasters results in altered placental transcriptome, which may be related to long-term emotional and behavioral consequences.
2022-05-25 | GSE197697 | GEO
Project description:Following a prenatal stress model, we collected RNA from ileum of offspring at 2 weeks of age. We sequenced the RNA to identify genes that are differentially expressed compared to offspring from unstressed controls. We identified DEGs and a number of biological and signaling pathways in the offsping in response to gesstational stress. We discuss the implications of these stress-induced genes on the development of inflammatory diseases in the gut of the offsping.
2020-06-08 | GSE151966 | GEO
Project description:RNASeq analysis of offspring ileum tissue following Prenatal stress
| PRJNA637902 | ENA
Project description:Reportedly, titanium dioxide nanoparticle exposure during pregnancy can affect the development of the central nervous system in mouse offspring; however, the underlying mechanism remains unknown. We investigated the impact of prenatal dioxide nanoparticle exposure on mRNA expression patterns in the brains of neonatal mice. Pregnant C57BL/6J mice were intratracheally administered a dioxide nanoparticle suspension (100 ug/mouse) on gestational day 10.5, and brains were collected from male and female offspring at day 1 postpartum. Total RNA was obtained, and mRNA expression profiles were comprehensively assessed using microarray analysis. The results showed 88 and 89 genes were upregulated (≥ 1.5-fold) accompanied by demethylation of CpG islands, whereas 13 and 33 genes were downregulated (≤ 0.67-fold) accompanied by demethylation of CpG islands in male and female offspring mice, respectively. Gene Set Enrichment Analysis (GSEA) revealed that these genes were enriched in gene ontology terms related to the regulation of transcription factors, cell proliferation, and organism development. Additionally, MeSH terms related to stem cells and morphogenesis were enriched.
2021-10-04 | GSE178199 | GEO
Project description:prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype. Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed. Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level. Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction. total samples analysed are 12
2011-12-12 | E-GEOD-26025 | biostudies-arrayexpress
Project description:Background: Prenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Although epigenetic processes may be responsible for PNMS effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can provide models of prenatal stress. Methods: Five months after the 1998 Quebec ice storm we recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, we investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8. Results: Prenatal maternal objective hardship was correlated with DNA methylation levels in 1675 CGs affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG5 and LTA, both highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells (PBMCs) and saliva cells. Conclusions: These data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. By using a natural disaster model, we can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress. Bisulphite converted DNA from the 34 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2
2015-08-26 | E-GEOD-72354 | biostudies-arrayexpress
Project description:Prenatal stress (PS) could cause depression of offprsing. Here, relative quantitative phosphoproteomics of hippocampus of PS-S and CON offspring rats were performed using LC-MS/MS to confirm known pathways and identify new areas of depression. A total of 6,790 phosphopeptides, 9,817 phosphorylation sites and 2978 phosphoproteins were detected. Among the 2978 phosphoproteins, 1760 (59.09%) with more than two phosphorylated sites, ENSRNOP00000023460 protein has more than 117 phosphorylated sites, and the average distribution of modification sites per 100 amino acids was 2.97. There were 197 different phophpeptides, including 140 increased phosphopeptides and 57 decreased phosphopeptides in PS-S offspring rats when compared to the CON offspring rats. These differential phosphopeptides corresponded to 100 upregulated and 44 downregulated phosphoproteins respectively. GO enrichment analysis these different phosphoproteins in the first five enrichments of CC category, MF category and BP category were involved in a total of 35 different phosphoproteins and these phosphoproteins were mainly related to myelin, microtubule and synapse associated proteins. The first five enrichment of KEGG pathways were found to be involved in many essential biological pathways, and the first five pathways included amphetamine addiction, insulin secretion, cushing syndrome and circadian entrainment signaling pathway. And these first five pathways were related to nine proteins including Adcy9, Apc, Cacna1c, Camk2a, Camk2b, Camk2g, Ctnnd2, Grin2a, Stx1a. Further research is needed to understand the precise role of these pathways in the depressive-like behavior of offspring rats caused by PS.
2021-12-30 | PXD019117 | Pride
Project description:Fetal Alcohol Spectrum Disorder (FASD) encompasses the deleterious consequences of Prenatal Alcohol Exposure (PAE), including developmental delay, dysmorphologies, cognitive and behavioral issues. The dose and timing of alcohol exposure, maternal and environmental factors, and genetics all impact FASD outcomes, but differential susceptibility to PAE remains poorly understood. In this study, we examined the differential effects of PAE on mouse brain development by measuring brain weight in embryos (embryonic day 14, E14) and neonatal pups (postnatal day 0, P0) exposed alcohol during early development. We used transcriptomics to determine whether offspring differentially affected by PAE also differ in gene expression. PAE offspring were classified as normal, middle, and low-weight brains relative to controls. The normal-weight brains showed no differences in gene expression, suggesting these offspring were both phenotypically and transcriptionally unaffected by PAE. While both middle- and low-weight brains showed changes in gene expression, the middle-weight brains showed the most robust transcriptome differences. In affected E14 offspring, we saw an upregulation of cell cycle and apoptosis by PAE, whereas at P0, we saw a downregulation of metabolic processes. Overall, these findings highlight variability in response to PAE and demonstrate the molecular processes involved in offspring affected by alcohol.
2024-12-06 | GSE267633 | GEO