Infant Circulating MicroRNAs as Biomarkers of Effect in Fetal Alcohol Spectrum Disorders
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE164209 | GEO | 2021/01/14
REPOSITORIES: GEO
Similar Datasets
Project description:Infant Circulating MicroRNAs as Biomarkers of Effect in Fetal Alcohol Spectrum Disorders
| PRJNA689559 | ENA
Project description:Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on bacille Calmette-Guerin (BCG) vaccine-induced responses in Ugandan infants. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n=42) and six (n=51) weeks after BCG immunisation using microarray. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. Maternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile.
2016-10-12 | GSE87801 | GEO
Project description:Prenatal alcohol exposure is the leading preventable cause of behavioural and cognitive deficits, which may affect between 2-5% of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with Fetal Alcohol Spectrum Disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Genome-wide DNA methylation patterns of buccal epithelial cells were analyzed using the Illumina HumanMethylation450 array on a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. After correcting for the effects of genetic background, 658 significantly differentially methylated sites between FASD cases and controls remained, with 41 displaying differences in beta greater than 5%. Furthermore, 203 differentially methylated regions containing 2 or more CpGs were also identified, overlapping with 167 different genes. The majority of differentially methylated genes were highly expressed in samples from the Allen Brain Atlas, which showed high correlations with buccal cell DNA methylation patterns. Furthermore, over-representation analysis of the up-methylated genes displayed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. These findings suggest that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.
2017-04-13 | GSE80261 | GEO
Project description:Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. This is particularly true for patients suffering from Fetal Alcohol Spectrum Disorders (FASD) who exhibit a wide range of cognitive deficiencies including impaired motor skill development. While these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We have previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells lead to altered gene expression in their descendant neurons at the single-cell level. Among the altered genes, we found that an increase of the calcium-activated potassium channel Kcnn2 in subset neurons in the motor cortex correlates with motor skill learning deficits in the mouse model of FASD. We further show that postnatal blocking of Kcnn2 improves these learning deficits. These results propose Kcnn2 blockers as a novel intervention for learning disabilities in FASD and possibly for other neurocognitive conditions.
2021-08-30 | GSE141714 | GEO
Project description:Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs (exmiRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed exmiRNAs with clinically-relevant effect sizes (Cohen's d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of exmiRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered exmiRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant exmiRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.
| S-EPMC7809131 | biostudies-literature
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:Alcohol exposure is known to impact several components of the one-carbon metabolism pathway, which is vital for providing methyl groups for DNA and peptide synthesis and for methylation modification of nucleotides and proteins. Methylation patterning in DNA is known to be altered across generations in specific situations in humans, including nutrient deprivation and smoking during pregnancy. We were interested in seeing whether heavy alcohol exposure during pregnancy, which is associated with fetal alcohol syndrome, influences genome-wide infant methylation patterning. From Guthrie card spots across over 100 infants of various genders, ethnicities, and maternal smoking and drinking status, we find two loci that are have significantly different methylation patterning associated with maternal drinking; cgXXX and cgYYY, the former near MCOLN3 and the latter in intergenic space. We also use available epidemiological information associated with our data set to replicate maternal smoking with infant methylation changes as well as replicate and expand upon methylation differences between genders and ethnicities.
2016-01-29 | GSE65428 | GEO
Project description:91 preterm infant gut metaproteomes measured in technical duplicate using an eleven salt pulse 2D-LC-MS/MS method. Samples represent 17 preterm infants over the first several weeks of life, of which 6 preterm infants eventually developed necrotizing enterocolitis.
| MSV000086096 | MassIVE
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 Whole brain tissue was harvested from day 70 fetal alcohol exposed males and matched controls for RNA extraction and hybridization to affymetrix miRNA 2.0 arrays. We obtained tissue from four models: Trimiester 1,2, and 3, injections and contious preference drinking.
2011-12-14 | E-GEOD-34413 | biostudies-arrayexpress
Project description:Acute Lymphoblastic Leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence of MLL translocations which is associated with a poor prognosis. Contributing to this poor prognosis is cellular drug resistance, especially to glucocorticoids like prednisolone. Although in vitro prednisolone resistance mechanisms have been proposed in pediatric ALL, it has never been studied in MLL-rearranged infant ALL, which are highly resistant to glucocorticoids in vitro and in vivo. We analyzed primary MLL-rearranged infant ALL expression profiles, which were either in vitro prednisolone-resistant or prednisolone-sensitive, in order to study in vitro prednisolone resistance.
2011-10-12 | E-GEOD-32962 | biostudies-arrayexpress