Prenatal alcohol exposure: profiling developmental DNA methylation patterns in central and peripheral tissues
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ABSTRACT:
PROVIDER: PRJNA497836 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8084460_1.fastq.gz | Fastqsanger.gz | |||
| SRR8084460_2.fastq.gz | Fastqsanger.gz | |||
| SRR8084470_1.fastq.gz | Fastqsanger.gz | |||
| SRR8084470_2.fastq.gz | Fastqsanger.gz | |||
| SRR8084480_1.fastq.gz | Fastqsanger.gz |
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Project description:Prenatal alcohol exposure (PAE) alters the development of neurobiological systems, leading to lasting neuroendocrine, neuroimmune, and neurobehavioral deficits. Although the etiology of this reprogramming remains unknown, emerging evidence suggests DNA methylation as a potential mediator and biomarker for the effects of PAE due to its responsiveness to environmental cues and relative stability over time. Here, we utilized a rat model of PAE to examine the DNA methylation profiles of rat hypothalami and leukocytes at four time points during early development to assess the genome-wide impact of PAE on the epigenome and identify potential biomarkers of PAE. Our model of PAE approximates to 1-2x the legal limit of drunk driving in most jurisdictions (blood alcohol 80-150 mg/dl) throughout the equivalent of the first two trimesters of human pregnancy. Hypothalami were analyzed on postnatal (P) days 1, 8, 15, 22 and leukocytes at P22 to compare central and peripheral markers. Genome-wide DNA methylation analysis was performed by methylated DNA immunoprecipitation followed by next-generation sequencing. PAE resulted in lasting changes to DNA methylation profiles across all four ages, with 118 differentially methylated regions (DMRs) displaying persistent alterations across the developmental profile at a false-discovery rate (FDR) <0.05. By contrast, 299 DMRs showed the same direction of change in the hypothalamus and leukocytes of P22 pups at an FDR<0.05, with some genes overlapping with the developmental profile findings. The majority of these DMRs were located in intergenic regions, which contained several computationally-predicted transcription factor binding sites. Differentially methylated genes were generally involved in immune function, epigenetic remodeling, metabolism, and hormonal signaling, as determined by gene ontology analyses. Persistent DNA methylation changes in the hypothalamus may be associated with the long-term deficits observed in PAE. Furthermore, correlations between epigenetic alterations in peripheral tissues and those in the brain will provide a foundation for the development of biomarkers of fetal alcohol spectrum disorder (FASD). Finally, findings from studies of PAE provide important insight into the etiology neurodevelopmental and mental health disorders, as they tend to share numerous symptoms and comorbidities.
2018-10-23 | GSE121582 | GEO
Project description:Background: Prenatal alcohol exposure (PAE) can alter the development of neurobiological systems, leading to lasting neuroendocrine, neuroimmune, and neurobehavioral deficits. Although the etiology of this reprogramming remains unknown, emerging evidence suggests DNA methylation as a potential mediator and biomarker for the effects of PAE due to its responsiveness to environmental cues and relative stability over time. Here, we utilized a rat model of PAE to examine the DNA methylation profiles of rat hypothalami and leukocytes at four time points during early development to assess the genome-wide impact of PAE on the epigenome and identify potential biomarkers of PAE. Our model of PAE resulted in blood alcohol levels of ~80-150 mg/dl throughout the equivalent of the first two trimesters of human pregnancy. Hypothalami were analyzed on postnatal days (P) 1, 8, 15, 22 and leukocytes at P22 to compare central and peripheral markers. Genome-wide DNA methylation analysis was performed by methylated DNA immunoprecipitation followed by next-generation sequencing. Results: PAE resulted in lasting changes to DNA methylation profiles across all four ages, with 118 differentially methylated regions (DMRs) displaying persistent alterations across the developmental period at a false-discovery rate (FDR) < 0.05. In addition, 299 DMRs showed the same direction of change in the hypothalamus and leukocytes of P22 pups at an FDR < 0.05, with some genes overlapping with the developmental profile findings. The majority of these DMRs were located in intergenic regions, which contained several computationally-predicted transcription factor binding sites. Differentially methylated genes were generally involved in immune function, epigenetic remodeling, metabolism, and hormonal signaling, as determined by gene ontology analyses. Conclusions: Persistent DNA methylation changes in the hypothalamus may be associated with the long-term physiological and neurobehavioral alterations in observed in PAE. Furthermore, correlations between epigenetic alterations in peripheral tissues and those in the brain will provide a foundation for the development of biomarkers of fetal alcohol spectrum disorder (FASD). Finally, findings from studies of PAE provide important insight into the etiology of neurodevelopmental and mental health disorders, as they share numerous phenotypes and comorbidities.
| S-EPMC6290329 | biostudies-literature
Project description:Prenatal exposure to ethanol can cause fetal alcohol spectrum disorder (FASD), a prevalent and preventable pediatric disorder. Identifying genetic risk alleles for FASD is impossible in human populations, but the Drosophila genetic model can provide insights. We analyzed changes in genome-wide gene expression in 96 wild-derived inbred fly lines after exposure to alcohol during development. We found extensive sexual dimorphism in the effect of alcohol on gene expression along with effects on adult locomotor activity and sleep. Genetic networks associated with changes in gene expression include both protein-coding and non-coding transcripts, including a female-specific module of small nucleolar RNAs that regulate pseudouridylation of ribosomal RNA. These data support a regulatory role for non-coding elements in response to developmental alcohol exposure.
2022-03-15 | GSE186240 | GEO
Project description:Prenatal adversity or stress can have long-term consequences on developmental trajec-tories and health outcomes. Although the biological mechanisms underlying these effects are poorly understood, epigenetic modifications, such as DNA methylation, have the potential to link early-life environments to alterations in physiological systems, with long-term functional impli-cations. We investigated the consequences of two prenatal insults, prenatal alcohol exposure (PAE) and food-related stress, on DNA methylation profiles of the rat brain during early devel-opment. As these insults can have sex-specific effects on biological outcomes, we analyzed epige-nome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cogni-tion, executive function, and behavior, of both males and females. We found sex-dependent and sex-concordant influences of these insults on epigenetic patterns. These alterations occurred in genes and pathways related to brain development and immune function, suggesting that PAE and food-related stress may reprogram neurobiological/physiological systems partly through central epigenetic changes, and may do so in a sex-dependent manner. Such epigenetic changes may re-flect the sex-specific effects of prenatal insults on long-term functional and health outcomes and may have important implications for understanding possible mechanisms underlying fetal alco-hol spectrum disorder and other neurodevelopmental disorders.
2021-11-01 | GSE186840 | GEO
Project description:Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in new-born pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.
2024-07-30 | GSE273157 | GEO
Project description:Maternal ethanol consumption during pregnancy is one of the main causes of Neurodevelopmental disorders (NDD). Prenatal alcohol exposure (PAE) produces several adverse manifestations. Even low or moderate intake has been associated with long lasting behavioral and cognitive impairment in offspring. In this study we examined the gene expression profile in the rat nucleus accumbens using microarrays, comparing animals prenatally exposed to ethanol and controls. The microarray gene expression showed an overall downward regulatory effect of PAE. Gene cluster analysis reveals that the main affected gene groups are related to transcription regulation, transcription factors and homeobox genes. We focus on the expression of the C-X-C motif chemokine ligand 16 (Cxcl16) which was differentially expressed. There is a significant reduction in the expression of this chemokine throughout the brain under PAE conditions, evidenced here by qPCR and immunohistochemistry. Chemokines are involved in neuroprotection and implicated in alcohol-induced brain damaged and neuroinflammation in the developing CNS, therefore, the significance of the overall decrease in Cxcl16 expression in the brain as a consequence of PAE, may reflect a reduced ability to neuroprotection against subsequent conditions, such as excitotoxic damage, inflammatory processes or even hypoxic-ischemic insult.
2020-10-30 | GSE160433 | GEO
Project description:Background: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete FreundM-bM-^@M-^Ys adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat. 192 samples, including 20 hybridization replicates
2014-11-21 | E-GEOD-63561 | biostudies-arrayexpress
Project description:Fetal alcohol exposure at any stage of pregnancy can lead to Fetal Alcohol Spectrum Disorder (FASD), a group of life-long conditions characterized by congenital malformations, as well as cognitive, behavioral, and emotional impairments. The teratogenic effects of alcohol have long been publicized; yet fetal alcohol exposure is one of the most common preventable causes of birth defects. Currently, alcohol abstinence during pregnancy is the best and only way to prevent FASD. However, alcohol consumption remains astoundingly prevalent among pregnant women; therefore, additional measures need to be made available to help protect the developing embryo before irreparable damage is done. Maternal nutritional interventions using methyl donors have been investigated as potential preventative measures to mitigate the adverse effects of fetal alcohol exposure. Here, we show that a single acute preimplantation (E2.5; 8-cell stage) fetal alcohol exposure in mice leads to long-term FASD-like morphological phenotypes (e.g., growth restriction, brain malformations, skeletal delays) in late-gestation embryos (E18.5) and demonstrate that supplementing the maternal diet with a combination of four methyl donor nutrients, folic acid, choline, betaine, and vitamin B12, prior to conception and throughout gestation effectively reduces the incidence and severity of alcohol-induced morphological defects without altering DNA methylation status and regulation of imprinting control regions. This study clearly supports that preimplantation embryos are vulnerable to the teratogenic effects of alcohol, emphasizing the dangers of maternal alcohol consumption during early gestation, and provides a potential proactive maternal nutritional intervention to minimize FASD progression, reinforcing the importance of adequate preconception and prenatal nutrition.
2023-01-23 | GSE222974 | GEO
Project description:Prenatal Alcohol Exposure in Rats Diminish Postnatal Cxcl16 Chemokine Ligand Brain Expression
| PRJNA673193 | ENA
Project description:Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician’s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta–cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic “placenta–cortex” signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ “placenta–cortex” signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta–cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein–protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that “intercellular communication” was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors. Protein validation experiments involving Western blot for one ligand–receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta–cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.
2023-09-01 | GSE241836 | GEO