Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE229266 | GEO | 2023/04/10
REPOSITORIES: GEO
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Project description:Background: Iron deficiency (ID) during the fetal-neonatal period results in long-term neurodevelopmental impairments associated with pervasive hippocampal gene dysregulation. Prenatal choline supplementation partially normalizes these effects, suggesting an interaction between iron and choline in hippocampal transcriptome regulation. To understand the regulatory mechanisms, we investigated epigenetic marks of genes that are poised to be activated (ATAC-seq) or repressed (H3K9me3 ChIP-seq) in iron-repleted adult rats having experienced fetal-neonatal ID exposure with or without prenatal choline supplementation. Results: Fetal-neonatal ID was induced by limiting maternal iron intake from gestational day (G) 2 through postnatal day (P) 7. Half of the pregnant dams were given supplemental choline (5.0 g/kg) from G11-18. This resulted in 4 groups at P65 (Iron-sufficient [IS], Formerly Iron-deficient [FID], IS with choline [ISch], and FID with choline [FIDch]). Hippocampi were collected from P65 iron-repleted male offspring and analyzed for chromatin accessibility and H3K9me3 enrichment. 22% and 24% of differentially transcribed genes in FID- and FIDch-groups, respectively, exhibited significant differences in chromatin accessibility, whereas 1.7% and 13% exhibited significant differences in H3K9me3 enrichment. These changes mapped onto gene networks regulating synaptic plasticity, neuroinflammation, and reward circuits. Motif analysis of differentially modified genomic sites revealed significantly stronger choline effects than early-life ID and identified multiple epigenetically modified transcription factor binding sites. Conclusions: This study reveals genome-wide, stable epigenetic changes and epigenetically modifiable gene networks associated with specific chromatin marks in the hippocampus, and lays a foundation to further elucidate iron-dependent epigenetic mechanisms that underlie the long-term effects of fetal-neonatal ID, choline, and their interactions.
2024-03-14 | GSE244206 | GEO
Project description:Background: Iron deficiency (ID) during the fetal-neonatal period results in long-term neurodevelopmental impairments associated with pervasive hippocampal gene dysregulation. Prenatal choline supplementation partially normalizes these effects, suggesting an interaction between iron and choline in hippocampal transcriptome regulation. To understand the regulatory mechanisms, we investigated epigenetic marks of genes that are poised to be activated (ATAC-seq) or repressed (H3K9me3 ChIP-seq) in iron-repleted adult rats having experienced fetal-neonatal ID exposure with or without prenatal choline supplementation. Results: Fetal-neonatal ID was induced by limiting maternal iron intake from gestational day (G) 2 through postnatal day (P) 7. Half of the pregnant dams were given supplemental choline (5.0 g/kg) from G11-18. This resulted in 4 groups at P65 (Iron-sufficient [IS], Formerly Iron-deficient [FID], IS with choline [ISch], and FID with choline [FIDch]). Hippocampi were collected from P65 iron-repleted male offspring and analyzed for chromatin accessibility and H3K9me3 enrichment. 22% and 24% of differentially transcribed genes in FID- and FIDch-groups, respectively, exhibited significant differences in chromatin accessibility, whereas 1.7% and 13% exhibited significant differences in H3K9me3 enrichment. These changes mapped onto gene networks regulating synaptic plasticity, neuroinflammation, and reward circuits. Motif analysis of differentially modified genomic sites revealed significantly stronger choline effects than early-life ID and identified multiple epigenetically modified transcription factor binding sites. Conclusions: This study reveals genome-wide, stable epigenetic changes and epigenetically modifiable gene networks associated with specific chromatin marks in the hippocampus, and lays a foundation to further elucidate iron-dependent epigenetic mechanisms that underlie the long-term effects of fetal-neonatal ID, choline, and their interactions.
2024-03-14 | GSE244207 | GEO
Project description:Preterm birth is often predisposed by chorioamnionitis (CA) and CA affects the fetal gut and lungs via intra-amniotic (IA) inflammation, thus accentuating the proinflammatory effects of preterm birth. It is not known if IA inflammation also affects other perfusion-sensitive organs (e.g., kidneys) before and after preterm birth. Using preterm pigs as model for preterm infants, we hypothesized that CA induces fetal and neonatal renal dysfunctions that can intially be detected via plasma proteome, partly explaining the frequent renal dysfunction in preterm infants. Fetal pigs (88% gestation) were given an IA dose of lipopolysaccharide (LPS, 1 mg/kg, n=28), delivered preterm by cesarean section three days later, and compared with controls (CON, n=26) at birth and postnatal day five. Plasma proteome and protein markers of inflammatory pathways were evaluated.
2021-03-25 | PXD014619 | Pride
Project description:Choline and methionine/choline deficient diets are widely used to generate severe rodent hepatic steatosis and steatohepatitis in an attempt to reflect stages of human non-alcoholic fatty liver disease (NAFLD). The underlying mechanism of hepatic injury in these models, and how this reflects human disease remains incompletely understood. We used detailed transcriptional analysis to interrogate the molecular mechanisms of this intervention and its similarity to human disease. Adult C57Bl/6J mice were maintained on control, choline deficient (CDD) or methionine/choline deficient (MCDD) diets for 4 weeks. Isolated liver RNA was used for transcriptional profiling by micro array analysis.
2016-06-01 | E-MTAB-3943 | biostudies-arrayexpress
Project description:To explore the influence of maternal choline intake on placental gene expression, we employed whole genome microarray expression profiling to identify genes that were differentially expressed in placental tissues obtained from women consuming two different doses (480 vs. 930 mg/d) of choline throughout the third trimester of pregnancy. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d. Full thickness placental samples were collected at delivery to extract RNA and perform the arrays. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d for 12 weeks. Placental samples were obtained at delivery
2012-07-12 | E-GEOD-39290 | biostudies-arrayexpress
Project description:Abstract: Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assess the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community to lack a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria show increased susceptibility to metabolic disease. Furthermore, bacterially-induced reduction of methyl-donor availability alters global DNA methylation patterns in both adult mice and their offspring in utero and engenders anxious behavior. Altogether, our results reveal an underappreciated aspect of bacterial choline metabolism (i.e., methyl-donor depletion) that is linked to alterations in metabolism, epigenetics, and behavior. More broadly, this work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal levels of nutrient intake.
2017-07-28 | GSE100983 | GEO
Project description:Liver fibrosis is a critical global health challenge, often leading to severe liver diseases without timely intervention. Choline deficiency has been linked to metabolic dysfunction associated steatohepatitis (MASH) and liver fibrosis, suggesting choline supplementation as a potential therapeutic approach. This study aimed to explore the therapeutic potential of choline supplementation in liver fibrosis resolution and its effects on cholesterol homeostasis using a mouse model with induced liver fibrosis. Our findings reveal that choline supplementation significantly decreases blood lactate dehydrogenase (LDH) and non-high-density lipoprotein cholesterol (non-HDL-C) levels. Transcriptome analysis showed that choline supplementation primarily induces genes related to cholesterol homeostasis, suggesting a significant impact on liver cholesterol synthesis. However, choline supplementation did not significantly alter the expression of fibrosis-related, choline metabolism-related, or epigenetics-related genes. This study provides novel insights into the role of choline in liver health and cholesterol metabolism, potentially informing treatments for liver fibrosis and related conditions.
2024-09-04 | GSE261310 | GEO
Project description:Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa. Among the diverse nutrients it can utilize is choline, which can be converted into the osmoprotectant glycine betaine and further catabolized as a source of carbon and nitrogen, similar to P. aeruginosa. Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis. In this study, we showed that multiple glutamine amidotransferase1 (GATase1)-containing AraC-family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to compare the acquisition and regulation of this pathway during environmental growth and infection.
2016-07-12 | GSE81652 | GEO
Project description:The objective of this study is to explore gene expression profiles of liver tissues in response to choline defficient diet by DNA microarray data analysis. Male CD-1mice (5 weeks) were fed either a choline-deficient diet (F2CDD, Oriental Yeast) or F2CDD plus 0.2% choline bitartrate for 3 weeks. Liver tissue from control versus choline-deficient samples were analyzed for gene expression on an Agilent Whole Mouse Genome Microarray.
2016-02-25 | E-GEOD-78053 | biostudies-arrayexpress
Project description:To explore the influence of maternal choline intake on placental gene expression, we employed whole genome microarray expression profiling to identify genes that were differentially expressed in placental tissues obtained from women consuming two different doses (480 vs. 930 mg/d) of choline throughout the third trimester of pregnancy. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d. Full thickness placental samples were collected at delivery to extract RNA and perform the arrays.
2012-07-13 | GSE39290 | GEO