Prenatal Alcohol Exposure in Rats Diminish Postnatal Cxcl16 Chemokine Ligand Brain Expression
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ABSTRACT:
PROVIDER: PRJNA673193 | ENA |
REPOSITORIES: ENA
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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: Not available
| S-EPMC7765294 | biostudies-literature
Project description:Growth restriction, craniofacial dysmorphology and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal and/or postnatal, but the underlying mechanisms remain unknown. We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome, e.g. craniofacial changes and growth restriction in adolescent mice. Here we further characterize the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of non-fostered ethanol-exposed and control mice at postnatal day 28. We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiological result of ethanol exposure in utero. We also find that, despite some catch-up growth after five weeks of age, the effect extends into adulthood, consistent with longitudinal studies in humans. Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis and lipid metabolism. Gene expression changes in the livers of offspring exposed to alcohol in utero compared to controls.
2010-09-30 | E-GEOD-23106 | biostudies-arrayexpress
Project description:Growth restriction, craniofacial dysmorphology and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal and/or postnatal, but the underlying mechanisms remain unknown. We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome, e.g. craniofacial changes and growth restriction in adolescent mice. Here we further characterize the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of non-fostered ethanol-exposed and control mice at postnatal day 28. We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiological result of ethanol exposure in utero. We also find that, despite some catch-up growth after five weeks of age, the effect extends into adulthood, consistent with longitudinal studies in humans. Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis and lipid metabolism. Gene expression changes in the kidneys of offspring exposed to alcohol in utero compared to controls.
2010-10-01 | E-GEOD-23105 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE23105: Postnatal Growth Restriction and Gene Expression Changes in a Mouse Model of Fetal Alcohol Syndrome (Kidney) GSE23106: Postnatal Growth Restriction and Gene Expression Changes in a Mouse Model of Fetal Alcohol Syndrome (Liver) Refer to individual Series
2010-09-30 | E-GEOD-23115 | biostudies-arrayexpress
Project description:Fetal alcohol spectrum disorders (FASD) are common, seen in 1-5% of the population in the United States and Canada. Regrettably, children diagnosed with FASD are not likely to remain with their biological parents, facing early maternal separation and foster placements throughout childhood. We have modeled FASD in mice via prenatal alcohol exposure and further induce early life stress through maternal separation. We report an association between adult hippocampal gene expression and prenatal and postnatal treatment that is related to behavioral changes. Clustering of expression profiles through weighted gene co-expression network analysis (WGCNA) identifies a set of transcripts associated with anxiety-like behavior as well as treatment group. Genes in this module are overrepresented by genes involved in transcriptional regulation and other pathways related to neurodevelopment. Interestingly, one member of this module, Polr2a, polymerase (RNA) II (DNA directed) polypeptide A, is downregulated by the combination of prenatal ethanol and postnatal stress in an RNA-Seq experiment and qPCR validation. Together, transcriptional control is implicated as a potential underlying mechanism leading to anxiety-like behavior via environmental insults. Greater understanding of the role of prenatal alcohol exposure and postnatal stress in altering the hippocampal transcriptome in the hippocampus is warranted. Further research is required to elucidate the mechanism involved and use this insight towards early diagnosis and amelioration strategies involving children born with FASD.
2019-06-27 | GSE133369 | GEO
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
Project description:Growth restriction, craniofacial dysmorphology and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal and/or postnatal, but the underlying mechanisms remain unknown. We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome, e.g. craniofacial changes and growth restriction in adolescent mice. Here we further characterize the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of non-fostered ethanol-exposed and control mice at postnatal day 28. We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiological result of ethanol exposure in utero. We also find that, despite some catch-up growth after five weeks of age, the effect extends into adulthood, consistent with longitudinal studies in humans. Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis and lipid metabolism.
2010-10-01 | GSE23105 | GEO
Project description:Growth restriction, craniofacial dysmorphology and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal and/or postnatal, but the underlying mechanisms remain unknown. We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome, e.g. craniofacial changes and growth restriction in adolescent mice. Here we further characterize the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of non-fostered ethanol-exposed and control mice at postnatal day 28. We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiological result of ethanol exposure in utero. We also find that, despite some catch-up growth after five weeks of age, the effect extends into adulthood, consistent with longitudinal studies in humans. Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis and lipid metabolism.
2010-10-01 | GSE23106 | 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