Transcription profiling of blood cells from rats fed a folate deficient diet vs fed a normal diet for 28 days
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
DISEASE(S): folate deficiency
SUBMITTER: Liselotte Ebbesen
PROVIDER: E-MEXP-154 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Previous studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. We used microarrays to compare MTHFR+/+ BALB/c mice fed control diet and MTHFR+/- BALB/c mice fed low folate diet. After weaning, 4 BALB/c Mthfr +/+ mice were fed with a control diet (CD, 2mg folate/kg) and 4 BALB/c Mthfr +/- mice were fed a low folate diet (FD, 0.3mg folate/kg) for 1 year. Both diets contain succinylsulfanthiozole (1%) to prevent folate synthesis by intestine microbial biota.
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Project description:We hypothesized that the availability of folate, a soluble B vitamin, would alter the levels of DNA methylation in spermatogenesis with consequences for the sperm epigenome and pregnancy outcomes. We fed male mice with either a folate-deficient or a folate-sufficient diet throughout life. Males fed the folate-deficient diet had offspring with increased birth defects, which included craniofacial and musculoskeletal malformations. These phenotypes corresponded to developmental genes with altered methylation in sperm. To determine if there was transmission of epigenetic effects from sires to offspring, global gene expression levels were assessed in placenta from 18.5 dpc fetuses sired by either a folate-sufficient or folate-deficient male. Gene expression was measured in placenta of 18.5 dpc fetuses sired by either a folate sufficient male (n=4 placentas from different litters and different fathers) or a folate deficient (FD) male (n=4 placentas from different litters and different fathers).
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Project description:Analysis of livers from 74-day old male rats fed vitamin A sufficient or vitamin A deficient diet for 53 days. Either 10ug or 2ug of total RNA used in standard Affymetrix protocol
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Project description:We investigated the nutritional effects on gene expression in sperm cells of F0 boars from a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs which were investigated in a previous study. The aim of this study was to investigate if the nutrition affects gene expression in sperm cells of differentially fed boars and thus carry information in the form of RNA molecules to the next generation. Four RNA samples from sperm cells of these differentially fed boars were analyzed by RNA-Seq methodology. We found no differential RNA expression in sperm cells of the two groups based on the adjusted P-value > 0.05. Nevertheless, we performed a pathway analysis with 105 genes that differed in gene expression on the level of nominal P-value < 0.05 between the two diet groups. We found a significant number of these differentially expressed genes were enriched for the pathway maps of bacterial infections in cystic fibrosis (CF) airways, glycolysis and gluconeogenesis p.3 and cell cycle_Initiation of mitosis. The GO processes including a significant portion of differentially expressed genes were viral transcription and viral genome expression, viral infectious cycle, cellular protein localization, cellular macromolecule localization, nuclear-transcribed mRNA catabolic process and nonsense-mediated decay. In summary, the results of the pathway analysis are also inconclusive and it is concluded that RNA expression in sperm cells is not significantly affected by extensive supplementation of methylating micronutrients. Consequently, RNA molecules could not be established as epigenetic marks in this feeding experiment. Gene expression in sperm cells from differentially fed F0 boars was measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars were used to study transgenerational epigenetic inheritance in a three generation pig pedigree. Therefore it was of interest if the diet affects gene expression in sperm cells which could then be transmitted to next generations.
2013-09-16 | E-GEOD-48777 | biostudies-arrayexpress
Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver transcriptome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. From a total of 44,000 probes for 26,456 genes, we found two gene clusters whose expression levels had statistically significant differences between control and deficient rats: 3,269 up-regulated and 2,841 down-regulated genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function. Modifications of gene expression in rat liver were measured in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates). Eight independent experiments were performed (4 Controls versus 4 Methyl Donor Deficiency - MDD).
2015-06-22 | E-GEOD-59039 | biostudies-arrayexpress
Project description:Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improving dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate and supplemented), and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P<0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding RARß, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log26 in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naïve rats. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling RBP4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change. All rats were housed in a room maintained at 22°C with a 12-h dark:light cycle, and food and water were freely available. For the Steady-State Vitamin A Study (experiment 1) and the Retinoic Acid 16-hour Kinetic Study (experiment 2), lactating female Sprague-Dawley rats with 12 female pups (purchased from Charles River Laboratories, Willmington, MA) were fed a vitamin A-deficient purified diet [AIN-93G diet, prepared by Research Diets, New Brunswick, NJ] to reduce the transfer of vitamin A in milk from mother to pups prior to the start of the study. For experiment 1, from weaning, the offspring were fed the same diet modified to contain vitamin A at one of four levels: 0 (vitamin A deficient), 0.4 mg retinol/kg diet (vitamin A marginal), 4 mg retinol/kg diet (vitamin A adequate control), or 100 mg retinol/kg diet (vitamin A supplemented). All rats were studied at 8 weeks of age. Rats were euthanized by carbon dioxide asphyxiation and blood and liver were collected rapidly and frozen in liquid nitrogen for storage at -80°C before analysis. In experiment 2, at 8 weeks of age female vitamin A-deficient rats were treated with ~100 ug of All-trans-Retinoic acid (at-RA) for 0 (vehicle only), 3, 6, 10 or 16 h (n=3-4/group). Tissues were collected and RNA was prepared in the same manner as in experiment 1. In the 90-minute "first pass" kinetic study (experiment 3), female rats were purchased at 6 weeks of age and fed a stock rodent diet. When the rats were 8 weeks old they were assigned to a control (naïve) group. Rats in the naive group received an equal amount of vehicle only (vegetable oil/5% ethanol). Food was removed immediately. Sixteen hours after priming, each rat was lightly anesthetized by isoflurane-oxygen inhalation and treated with ~25 ug all-trans-RA bound to albumin [10 ug RA per 100 g bo dy weight], injected into the exposed left common iliac vein. The incision was closed with a surgical staple. The rats were allowed to recover from the anesthesia. Rats were killed at 0 minute (vehicle injection), and 30, 60, and 90 min (n = 3/group) after injection of the RA test dose. Rats were euthanized by carbon dioxide asphyxiation and blood and liver were collected rapidly and frozen in liquid nitrogen for storage at -80°C before analysis. For experiment 1, five biological repeats were Vitamin A deficient, seven biological repeats were Vitamin A marginal, six biological repeats were Vitamin A adequate, and two biological repeats were Vitamin A supplemented. In experiment 2, three biological repeats were performed for each of the following treatments: untreated, at-RA for 3 hours, at-RA for 6 hours and at-RA for 16 hours. Four biological repeats were treated with at-RA for 10 hours. For experiment 3, two biological repeats were untreated and three biological repeats were performed for each of the following at-RA treatment times: 30, 60 and 90 minutes. A total of 47 samples were analyzed.
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Project description:We investigated the nutritional effects on gene expression in testes of F0 boars from a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs which were investigated in a previous study. The aim of this project was to investigate if the nutrition affects gene expression in testis of differentially fed boars and thus impact on spermatogenesis. We found a small number of 70 genes that were differentially expressed (fc ≥ 1) on the P<0.01 significance level. The false discovery rate (FDR) was 0.82 indicating that only a small portion of these genes are real positives. Nevertheless, we performed a pathway analysis and found this moderate differential expression associated with pathways maps of development_A2B receptor: action via G-protein alpha s, cell adhesion_Tight junctions and cell adhesion_Endothelial cell contacts by junctional mechanisms. The gene ontology (GO) processes that matched the gene expression data in boars’ testes were positive regulation of nucleobase-containing compound metabolic process, cellular response to hormone stimulus and cellular process. The pathway maps and GO processes associated with gene expression differences do not indicate a simple relationship between nutritional influences and gene expression in testes. Nevertheless the Adenosine A2B receptor influences cell differentiation and proliferation and has thus far reaching consequences. Similar applies to those GO processes positive regulation of nucleobase-containing compound metabolic process, cellular response to hormone stimulus and cellular process that were associated with differentially expressed genes between the testes samples. The expression result is thus not conclusive of whether the diet affects processes related to transmittable epigenetic marks. The results, however, indicate that the extreme supplementation of methylating micronutrients from month one to month ten of age has a very moderate (if any) effect on gene expression in boar testes as measured by microarray analysis. Gene expression in testes from differentially fed F0 boars was measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars were used to study transgenerational epigenetic inheritance in a three generation pig pedigree. Therefore it was of interest if the diet affects gene expression in testes and so could impact spermatogenesis.
2013-09-16 | E-GEOD-48597 | biostudies-arrayexpress
Project description:Previous studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. In addition, we reported that C57Bl/6J mice did not form tumors under the same conditions. We used microarrays to identify the genetic differences between BALB/c and C57Bl/6J mice that promote tumorigenesis in BALB/c mice. Two groups of mice will be used in the micro-array experiment. One group will consist of four BALB/c mice and the second group will consist of four C57Bl/6 mice. Both groups have mild MTHFR deficiency (Mthfr+/-) and will receive low folate diet (0.3 mg folate/kg) for one year. RNA samples will be extracted from duodenum, the first section of the small intestine where tumors were observed in BALB/c mice. Eight Affymetrix GeneChip Mouse Gene 1.0 ST Array Chips will be used in this experiment.
2013-04-09 | E-GEOD-34010 | biostudies-arrayexpress
Project description:The objective of this study is to determine the effect of maternal folate deficiency on the skeletal muscle transcriptome of piglets from a reciprocal cross, in which full-sibling Landrace (LR) and full-sibling Chinese local breed Laiwu (LW) pigs were used for reciprocal cross matings, and sows were fed either a folate deficient or a normal diet during early-mid gestation. In addition, the difference in the responsiveness of the piglets to folate deficiency during early-mid pregnancy between reciprocal cross groups was investigated.Longissimus dorsi (LD) muscle samples were collected from newborn piglets and a 4 x 44K Agilent porcine oligo microarray was used for transcriptome analysis of porcine LD muscle. The results showed that folate deficiency during early-mid pregnancy affected piglet body weight, LD muscle fiber number and content of intramuscular triglyceride.
2013-10-14 | E-MEXP-3996 | biostudies-arrayexpress