In search of epigenetic marks in testes and sperm cells of differentially fed boars
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ABSTRACT:
ORGANISM(S): Sus scrofa
SUBMITTER: Martin Braunschweig
PROVIDER: E-GEOD-48778 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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: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:We investigated the nutritional effects on gene expression in 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. Gene expression profiles showed significant twofold differences in mRNA level between 8 C F2 offspring and 8 E F2 offspring for 79, 64 and 53 probes for muscle, liver and kidney RNA, respectively. We found that in liver and muscle respective pathways of lipid metabolism and metabolic pathway were over-represented for the differentially expressed genes. Gene expression in three tissue types of F2 offspring from differentially fed F0 boars were measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars produced the F1 males that received exclusively the standard diet. The F2 generation was then produced with these F1 boars. Gene expression was measured in liver, skeletal muscle and kidney of 8 F2 pigs derived from F0 boars that received the standard diet and of 8 F2 pigs derived from those F0 boars that received the standard diet supplemented with methylating micronutrients.
2011-09-28 | E-GEOD-32412 | biostudies-arrayexpress
Project description:Cells of the osteoblast lineage affect homing, number of long term repopulating hematopoietic stem cells (HSCs) HSC mobilization and lineage determination and Blymphopoiesis . More recently osteoblasts were implicated in pre-leukemic conditions in mice. Yet, it has not been shown that a single genetic event taking place in osteoblastscan induce leukemogenesis. We show here that in mice, an activating mutation of β-catenin leading to development of acute myeloid leukemia (AML) with common chromosomal aberrationsand cell autonomous progression. Activated β-catenin stimulates expression of the Notch ligand Jagged-1 in osteoblasts. Subsequent activation of Notch signaling in HSCprogenitors induces the malignant changes. Demonstrating the pathogenetic role of theNotch pathway, genetic or pharmacological inhibition of Notch signaling ameliorates AML. Nuclear accumulation and increased β-catenin signaling in osteoblasts was also identified in 38% ofpatients with MDS/AML. These patients showed increased Notch signaling in hematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce AML, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeuticapproach to AML. The present entry describes a comparison of copy numbers of DNA from βcat(ex3)osb mice from the mouse spleen with that of WT (C57BL/J Mice) mice. DNA from spleen myeloid cells from βcat(ex3)osb mice and WT mice were hybridized to Agilent CGH 244A arrays. DNA from spleen myeloid cells from βcat(ex3)osb mice in C57BL/J background was labeled with red dye. DNA from spleen myeloid cells from WT (C57BL/J) mice were labeled with green dye. There were five arrays with DNA from 1 mouse of each genotype per array.
2014-01-21 | E-GEOD-51690 | biostudies-arrayexpress
Project description:Folate-mediated one-carbon metabolism is required for purine, thymidylate, and S-adenosylmethionine synthesis. Impairments in folate metabolism diminish cellular methylation potential and genome stability. Cytoplasmic serine hydroxymethyl transferase (cSHMT) regulates partitioning between thymidylate and SAM biosynthesis. These experiments were designed to determine if mutations in cSHMT led to alterations in gene expression. Keywords: genetic modification RNA was isolated from proximal colons of cSHMT mutant, heterozygous, and wild-type mice raised on a folate-deficient diet. Three colon samples were isolated from each genotype to provide biological replication. Mutant and heterozygous data were then compared pair-wise against wild-type expression data.
2010-03-03 | E-GEOD-14645 | biostudies-arrayexpress
Project description:Rationale: Low B12 has been shown to play an important role in the prediction of metabolic risk, but its significance and mechanism in the development of adiposity and adipose tissue dysfunction is largely unknown. Objective: To investigate the role of B12 and folic acid in the development of adipocyte dysfunction. Methods and Results: Microarray analysis of human adipocytes (CHUB-S7 cell line) cultured and differentiated in customised media with varying concentrations of B12 and folic acid led to the identification of two important pathways: cholesterol synthesis and unfolded protein response (UPR). Adipocytes cultured in media with low B12 (150 pmol/L) or no B12 had increased intracellular total cholesterol, higher secreted homocysteine levels, induced UPR and reduced glucose uptake capacity compared to adipocytes cultured in normal media with higher B12. The folate concentrations had either no or little effect on the measured functions. Further analysis of these adipocytes for overall DNA methylation showed that the promoter regions of sterol regulatory element-binding transcription factor 1 (SREBF1) and low density lipoprotein receptor (LDLR) were hypomethylated in the low and no B12 conditions. The SREB proteins (SREBP1 and 2) and mRNA expressions (SREBF1 and LDLR) were also increased in the same conditions. Conclusion: The data suggest that low B12 can lead to adipocyte dysfunction by inducing excess cholesterol biosynthesis, homocysteine production and induction of UPR and overall adipocyte dysfunction. Both of these pathways and adipocyte dysfunction play a significant role in the development of cardiovascular diseases. Independent replicate samples of the human adipocyte cell line CHUB-S7 were treated with four different concentrations of B12 and folate.
2012-12-30 | E-GEOD-43166 | biostudies-arrayexpress
Project description:Wistar Kyoto, inbred male rats (M & B, Ry, Denmark) were randomized and fed a semisynthetic pellet diet deficient in folate (TD350, Harland, Madison, Wisconsin, USA) or an identical diet with a normal amount of folate (TD351, Harland). Special analyses were performed to establish the content of Methionine, Vitamin B12, Folate and Vitamin B6 in the two diets. The folate content was <0.06 mg/kg and 1.63 mg/Kg, respectively. Detailed specification of the diets has been published previously. Animals were housed in stainless steel cages with a bed of sawdust, two to a cage, and were allowed free access to food and drinking water. The room temperature was 23a C and the humidity was 45-55 %. Light cycles consisted of 12 h light/12 h darkness. The animals were weighed at randomization and subsequently every seven days. The animal experiments were carried out in accordance with the guidelines of the International Scientific Committee for Thrombosis and Hemostasis, and the Danish Ethical Committee for Animal Experimentation had approved the study protocol. This study consisted of twelve rats fed the folate deficient diet and twelve rats fed the normal diet for 28 days.
2005-08-01 | E-MEXP-154 | biostudies-arrayexpress
Project description:Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline- and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J M-bM-^IM-^H C57BL/6J M-bM-^IM-^H C3H/HeJ < 129S1/SvImJ M-bM-^IM-^H CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor M-NM-1 (PPARM-NM-1)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPARM-NM-1-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice. Male A/J, C3H/HeJ and WSB/EiJ inbred mice were maintained on either control or choline- and folate-deficient (CFD) diets for 12 weeks. Gene expression profiles in the livers from control mice and mice fed a CFD-diet were investigated.
2014-10-16 | E-GEOD-62362 | 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. 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.
2013-12-03 | E-GEOD-34011 | biostudies-arrayexpress
Project description:Weanling rats fed a choline-deficient diet develop acute renal failure (ARF) after 6-7 days of receiving the experimental diet. Its pathogenesis is controversial. Menhaden oil has a protective effect in this experimental model. The aim of this study is to describe both the genetic profile and its changes when vegetable oils are replaced by menhaden oil. Wistar, weanling rats from the Animal Facility of the Centre of Experimental and Applied Pathology were divided into 4 groups and fed with the following diets: 1- Choline-deficient diet with vegetable oils as lipids (corn and hydrogenated oils); 2- Choline-supplemented diet with vegetable oils as lipids; 3- Choline-deficient diet with menhaden oil as lipid; and 4- Choline supplemented diet with menhaden oil as lipid. Animals were sacrificed after 6 days of receiving the experimental diets. The right kidney was cryopreserved. In this assay biological duplicated samples were used. In order to evaluate changes in gene expression WT Expression Kit (Ambion, USA) over the platform GeneChip® Gene 1.0 ST Rat Genome Array (Affymetrix Inc, USA) was used. Fluorescent distribution in the array was obtained using the language R (www-r-project.org), in house own algorithms and other formsbioconductor tools http://www.bioconductor.org/. We analyzed the differential gene expression, using as cut value p<0.01 with fdr control & |log FC|>1.5, in all groups. Rats fed with diets 2, 3 and 4 have similar genetic profiles. However, the comparison between rats fed with diets 2 and 4 showed 35 genes with diferential expression. As these rats did not have renal necrosis, we can hypothesize that the differential expression is due to the menhaden oil of the diet. In short, the massive analysis of genetic expression allowed to confirm that menhaden oil has a protective effect in this experimental model and to identify 35 genes that could be responsible of that protection. Twenty eight animals were sacrificed after 6 days of receiving the experimental diets. The right kidney was cryopreserved for microarray analysis. Cryopreserved kidney was pulverized under liquid-nitrogen conditions. Total RNA was purified from 30 mg of frozen rat kidney tissue. Each sample represents a pool of 3 animals (except CD+AM SN with 2 animals/pool), to reduce biological variation. In this assay biological duplicated samples were used.
2011-12-06 | E-GEOD-34139 | biostudies-arrayexpress