Persistent Alterations in the imprinted miRNA and snoRNA populations in mouse models of fetal alcohol spectrum disorders (FASD)
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Benjamin Laufer
PROVIDER: E-GEOD-34413 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We sought to characterize the persistnet changes in brain miRNAs across multiple mouse models of fetal alcohol exposure We used miRNA expression arrays to characterize and observe the deregulation of brain specific ncRNAs
2011-12-14 | GSE34413 | GEO
Project description:Prenatal alcohol exposure is recognized to alter DNA methylation profiles of brain cells during development, and as being part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol during the initial embryonic stages, a window marked with dynamic DNA methylation reprogramming, and on how this may rework the brain developmental program. Using a pre-clinical in vivo mouse model, we show that pre-implantation alcohol exposure leads to adverse developmental outcomes that replicate clinical facets observed in children with FASD. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinted control regions, and abnormal re-establishment of de novo DNA methylation profiles in various biological pathways (e.g, neural/brain development). These findings support the contribution of alcohol-induced DNA methylation programming deviations during pre-implantation to the manifestations of neurodevelopmental phenotypes associated with FASD.
2023-01-17 | GSE162765 | GEO
Project description:Moderate alcohol exposure during pregnancy can result in a heterogeneous range of neurobehavioural and cognitive effects, termed fetal alcohol spectrum disorders (FASD). We have developed a mouse model of FASD that involves moderate ethanol exposure throughout gestation achieved by voluntary maternal consumption. This model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that this leaves a long-term footprint on the adult brain. However, the long-term effects of prenatal ethanol exposure on brain gene expression, when behavioural phenotypes are apparent, are unclear. We used a microarray experiment and focused on the genes identified by both to evaluate the genome-wide alterations to the adult brain transcriptome caused by prenatal ethanol exposure. To generate samples, female C57BL/6J mice were given ethanol injections (2.5g/kg of ethanol in saline) twice on gestational days 8 and 11 to produce acute ethanol exposure effects. Control females were injected with the same volume of saline. Females were mated. Whole brain RNA from adult (postnatal day 70) male ethanol-exposed offspring was extracted. RNA samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice).
2011-12-16 | E-GEOD-34469 | biostudies-arrayexpress
Project description:Moderate alcohol exposure during pregnancy can result in brain gene expression changes in resulting offspring. We have developed a mouse model of FASD that involves moderate ethanol exposure in mid-gestation (trimester 2 equivalent) achieved by injections of ethanol. We have previously shown that this model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that there will be gene expression changes immediately following acute ethanol exposure in the fetal brain. We used a microarray experiment and focused on the genes identified to evaluate the genome-wide alterations to the fetal brain transcriptome caused by prenatal ethanol exposure. To generate samples, female C57BL/6J mice were given ethanol injections (2.5g/kg of ethanol in saline) twice on gestational days 14 and 16 to produce acute ethanol exposure effects. Control females were injected with the same volume of saline. Dams were sacrified on gestational day 16, following ethanol exposure, and whole brains from fetuses were then extracted. RNA was isolated from brain tissue and samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice).
2013-01-08 | E-GEOD-43324 | 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:Moderate alcohol consumption during pregnancy can result in a heterogeneous range of neurobehavioural and cognitive effects, termed fetal alcohol spectrum disorders (FASD). We have developed a mouse moder of FASD that involves moderate ethanol exposure throughout gestation achieved by voluntary maternal consumption. This model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that this leaves a long-term footprint on the adult brain. However, the long-term effects of prenatal ethanol exposure on brain gene expression, when behavioural phenotypes are apparent, are unclear. We used two independent microarray experiments and focused on the genes identified by both to evaluate the genome-wide alterations to the adult brain transcriptome caused by prenatal ethanol exposure via moderate maternal drinking. To generate samples, two independent groups of female C57BL/6J mice were given access to 10% ethanol in water or water only. Control females had access to water only. Females were mated and continued to drink from gestational day 0 to pup postnatal day 10. Whole brain RNA from adult (postnatal day 70) male ethanol-exposed offspring was extracted. For experiment 1, RNA samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice). For experiment 2, RNA from two mice were pooled per chip and three arrays per treatment were used (3 control, 3 ethanol, total n=12 mice).
2011-12-10 | E-GEOD-34305 | biostudies-arrayexpress
Project description:The developing brain is particularly sensitive to ethanol during the brain growth spurt or synaptogenesis (third human trimester equivalent). This has been shown to lead to abnormal brain development and behavioural changes in the adult mouse that are relevant to those seen in humans with fetal alcohol spectrum disorders (FASD). We evaluated the long-term (postnatal day 60 young adult) gene expression changes that occur in the brain due to ethanol exposure during synaptogenesis. We used microarray analyses to evaluate the changes in brain gene expression at postnatal day 60 that occur due to ethanol treatment at postnatal days 4 and 7 (synaptogenesis). To generate samples, C57BL/6J pups were injected with ethanol (experimental) or saline (control) at postnatal days 4 and 7. Pups were weaned at postnatal day 25 and sacrificed at postnatal day 60. Total RNA was extracted from whole brain tissue and RNA from three male mice from three different litters were pooled as one biological replicate. Each male ethanol-treated mouse represented in a sample was matched by a control littermate present in a control sample. This study consists of two biological replicates for each experimental group (total mice used was n=12).
2011-12-20 | E-GEOD-34549 | biostudies-arrayexpress
Project description:The developing brain is particularly sensitive to ethanol during the brain growth spurt or synaptogenesis (third human trimester equivalent). This has been shown to lead to abnormal brain development and behavioural changes in the adult mouse that are relevant to those seen in humans with fetal alcohol spectrum disorders (FASD). We evaluated the acute (4h post-treatment) gene expression changes that occur in the brain due to ethanol exposure during synaptogenesis (postnatal day 7). We used microarray analyses to evaluate the changes in brain gene expression at postnatal day 7 that occur due to ethanol treatment at postnatal day 7 (synaptogenesis). To generate samples, C57BL/6J pups were injected with ethanol (experimental) or saline (control) at postnatal day 7 (2 x 2.5 g/kg at 0h and 2h). Pups were sacrificed 4 hours following the initial injection. Total RNA was extracted from whole brain tissue and RNA from three male mice from three different litters were pooled as one biological replicate. Each male ethanol-treated mouse represented in a sample was matched by a control littermate present in a control sample. This study consists of two experimental (ethanol-treated) biological replicates and four control (saline vehicle-treated) replicates (total mice used was n=18).
2014-07-18 | E-GEOD-59512 | biostudies-arrayexpress
Project description:In this report we assessed alterations to adult mouse brain tissue by assaying DNA cytosine methylation and small noncoding RNA (ncRNA) expression, specifically the microRNA (miRNA) and small nucleolar RNA (snoRNA) subtypes. We found long lasting alterations in DNA methylation as a result of fetal alcohol exposure, specifically in the imprinted regions of the genome harboring ncRNAs and sequences interacting with regulatory proteins. ~20% of the altered ncRNAs mapped to three imprinted regions: Snrpn-Ube3a, Dlk1-Dio3, and Sfmbt2, which showed differential methylation and have been previously implicated in neurodevelopmental disorders. The findings of this report help to expand on the mechanisms behind the long lasting changes in the brain transcriptome of FASD individuals. Comparison of fetal alcohol exposed and matched control adult C57/BL6J mice brains with olfactory bulbs removed
2013-05-21 | E-GEOD-47111 | biostudies-arrayexpress
Project description:This study examined if p53 was essential in the brain’s response to alcohol using a mouse model of fetal alcohol spectrum disorder (FASD) that involved the equivalent of a single day of binge drinking. We quantified the amount of cell death in specific brain regions and examined the levels of gene expression in these regions 8 hours after alcohol exposure using RNA-seq. Contrary to expectations, we found that cell death still occurred at the same or greater level in the brains of mice lacking p53 as in normal mice. However, we also found evidence that the lack of p53 greatly affected the expression of groups of genes involved in brain cell communication and metabolism.
2017-09-05 | GSE100217 | GEO