A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice [MeDIP_chip]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE90499 | GEO | 2017/04/20
SECONDARY ACCESSION(S): PRJNA354934
REPOSITORIES: GEO
Similar Datasets
Project description:Evaluation of transgenerational influence of paternal dietary methyl substrates on offspring and grand-offspring brain and behavior Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (MD F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. These phenomena did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.
2017-04-20 | GSE90158 | GEO
Project description:BACKGROUND & AIMS: Inflammatory Bowel Diseases (IBD), including Crohnâ??s disease and ulcerative colitis, are chronic illnesses that are thought to develop secondary to a pathologic interaction between the immune system and the intestinal microflora that is manifested by the gut mucosa. IBD has been recognized as disorders in which developmental epigenetic changes, such as DNA methylation, may play an important pathogenic role. DNA methylation can be influenced in mammals by dietary exposures. A methyl-donor diet has been specifically found to be effective in inducing permanent changes in DNA methylation at certain genomic loci in murine models. Importantly, the methyl-donor substances utilized are routinely incorporated into prenatal micronutrient supplements for humans. In this study we addressed whether maternal exposure to a methyl-donor diet induces prolonged alterations in offspring colitis susceptibility and whether it leads to stable colonic mucosal epigenetic changes and gene expression alterations in mice. We also assessed whether the maternal methyl-donor diet induced persistent changes in the colonic microbiota in the offspring. METHODS: Colonic mucosa from offspring of mothers fed a methyl donor diet (MD) or control diet was interrogated by methylation specific amplification microarray (MSAM) at postnatal day 30 (P30) and P90 to screen for changes in DNA methylation, with bisulfite pyrosequencing validation. Transcriptomic changes in the same tissue were analyzed by microarray expression profiling and real time RT-PCR. The mucosal microbiome was studied by high throughput, detailed pyrosequencing of 16S rRNA. RESULTS: MD exposure during prenatal and early development lead to a significant increase in colitis susceptibility that persisted even after 69 days of diet reversal (P90). MD exposure also influenced DNA methylation and expression at select genomic loci. Overlap between DNA methylation and gene expression changes was confirmed at Ppara, a gene previously implicated in murine colitis. Metagenomic analyses failed to reveal consistent bacteriomic differences between the P30 and P90 age groups. CONCLUSIONS: Prenatal and early developmental exposure to MD induces increased colitis susceptibility, mucosal epigenomic, and transcriptomic changes that do not appear to associate with consistent microbiomic alterations. These findings underscore the importance of maternal nutrition on offspring colitis susceptibility in mammals and implicate the importance of the associated mucosal epigenetic modification. Our results bare potentially significant public health relevance as well. 4 independent MD versus control comparisons at P90 were performed as follows. RNA (0.4ug) samples were processed and labelled with Cy3 and Cy5 (Quick Amp labelling kit, two color, Agilent technologies) and 4 independent P90 MD to P90 control comparisons were done on Agilent technologies 4x44k whole genomic expression microarray G2519F, Amadid:014868)
2010-10-20 | E-GEOD-24354 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Inflammatory Bowel Diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic illnesses that are thought to develop secondary to a pathologic interaction between the immune system and the intestinal microflora that is manifested by the gut mucosa. IBD has been recognized as disorders in which developmental epigenetic changes, such as DNA methylation, may play an important pathogenic role. DNA methylation can be influenced in mammals by dietary exposures. A methyl-donor diet has been specifically found to be effective in inducing permanent changes in DNA methylation at certain genomic loci in murine models. Importantly, the methyl-donor substances utilized are routinely incorporated into prenatal micronutrient supplements for humans. In this study we addressed whether maternal exposure to a methyl-donor diet induces prolonged alterations in offspring colitis susceptibility and whether it leads to stable colonic mucosal epigenetic changes and gene expression alterations in mice. We also assessed whether the maternal methyl-donor diet induced persistent changes in the colonic microbiota in the offspring. METHODS: Colonic mucosa from offspring of mothers fed a methyl donor diet (MD) or control diet was interrogated by methylation specific amplification microarray (MSAM) at postnatal day 30 (P30) and P90 to screen for changes in DNA methylation, with bisulfite pyrosequencing validation. Transcriptomic changes in the same tissue were analyzed by microarray expression profiling and real time RT-PCR. The mucosal microbiome was studied by high throughput, detailed pyrosequencing of 16S rRNA. RESULTS: MD exposure during prenatal and early development lead to a significant increase in colitis susceptibility that persisted even after 69 days of diet reversal (P90). MD exposure also influenced DNA methylation and expression at select genomic loci. Overlap between DNA methylation and gene expression changes was confirmed at Ppara, a gene previously implicated in murine colitis. Metagenomic analyses failed to reveal consistent bacteriomic differences between the P30 and P90 age groups. CONCLUSIONS: Prenatal and early developmental exposure to MD induces increased colitis susceptibility, mucosal epigenomic, and transcriptomic changes that do not appear to associate with consistent microbiomic alterations. These findings underscore the importance of maternal nutrition on offspring colitis susceptibility in mammals and implicate the importance of the associated mucosal epigenetic modification. Our results bare potentially significant public health relevance as well.
2010-10-20 | GSE24354 | GEO
Project description:By comparing mouse fibroblasts from two parental strains (Bl6 and Spretus) with fibroblasts from their first generation offspring (F1) we can detect allele specific expression of proteins. The Bl6 and Spretus lines are evolutionary distant and harbour many SNPs in their genomes which when synonomous we can detect on the protein level using mass spectrometry. By mixing SILAC labeled Bl6, Spretus and F1 offspring cell lines we can detect peptides shared between all three cell lines and also SNP peptides that are only expressed in the F1 cells and either Bl6 or Spretus cells. By comparing the abundance of the shared peptides and the SNP peptides we can quantify how much of a protein in the F1 cells that comes from the paternal or maternal allele. This data were then further compared to polysome profiling data. Azidohomoalanine labeling was used to enrich newly synthesized proteins from the three cell lines.
2015-08-18 | PXD002337 | Pride
Project description:Poor parental health can influence the development and eventual health outcomes of their offspring. Many studies have detailed the maternal role yet a father’s health requires further examination as his poor nutritional status has also been shown to have negative consequences on fetal development and impact the long-term health of his offspring. The present study examined how preimplantation embryo development was altered by sub-optimal paternal diet, with specific focus on sperm- and seminal plasma-mediated mechanisms. To address this, male mice were fed a diet to model either under (low protein diet (LPD)) or over (high fat/sugar ‘Western’ diet (WD)) nutrition, LPD or WD supplemented with methyl-donors or a control diet (CD) before mating. Embryo development was assessed using in vitro time-lapse imaging of preimplantation embryos which revealed a significant increase in embryo development rates in all experimental groups when compared to CD embryos. Further analysis of the semen revealed a significant number of differentially expressed seminal plasma proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. This study highlights a role for paternal nutritional status influencing embryonic development and the maternal reproductive tract via changes to his metabolic and reproductive health. These findings demonstrate potential direct (sperm-mediated) and indirect (seminal plasma-mediated) pathways in which a father's poor diet could shape the long-term health of his offspring
2024-07-25 | PXD044980 | Pride
Project description:The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of reproductive age adults consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father’s poor nutritional status has been shown to have negative consequences on fetal growth and development and ultimately impact the long-term adult health of the offspring. In this study we examined sperm and seminal plasma mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. Male mice were fed a diet to model either under (low protein diet (LPD)) or over (high fat/sugar (Western) diet (WD)) nutrition, LPD or WD supplemented with methyl-donors or a control diet before mating with age-matched control fed females. Male metabolic health was influenced by WD and MD-WD; with significant changes in serum lipids and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35). In vitro embryo development was revealed all sub-optimal diets with and without methyl-donors increased the rate of embryo development. As embryo development can be directed by sperm and seminal plasma mediated mechanism, we also examined the proteomic profile of the seminal plasma, revealing a significant number of changes in all groups compared to control (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19). Male diet also altered uterine gene expression examined via qPCR, specifically alterations in Cd14 and Ptgs1 were observed in response to male WD matings. Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive factors, which can ultimately alter embryonic development and the post-mating maternal environment. This study highlights potential direct (sperm mediated) and indirect (semen mediated) pathways in which a father's poor diet could shape the long-term health of his offspring.
2024-07-18 | GSE241404 | GEO
Project description:Heterosis occurs where F1 offspring display superior characteristics to the parents. Heterosis is usually considered to result from crosses of genetically distinct (e.g. homozygous inbred) parents producing heterozygous F1 offspring. Most mechanistic models for heterosis require genetically heterozygous F1 hybrid offspring harbouring allelic diversity. Epigenetic or dosage models for heterosis could allow for heterosis effects in F1 offspring that display no allelic diversity with their parents. Reciprocal inter-ploidy crosses between diploid (2x) and tetraploid (4x) lines in the same genetic background generates genetically identical F1 triploids (3x). Such reciprocal F1 triploids differ according to whether the additional chromosome set is either maternally (maternal excess) or paternally inherited (paternal excess). Biomass accumulation and abiotic stress tolerance between the parental (2x and 4x) and reciprocal F1 triploid (3x) offspring of Arabidopsis thaliana accession C24 reveals a strong parental genome-dosage induced heterosis in the paternal-excess triploid F1 plants. In these F1 triploids, the circadian clock related genes CCA1 and TOC1, and the growth factors PIF4 and PIF5, display different expression levels compared to the non-heterotic maternal excess F1 triploid siblings. Whole transcriptome profiling reveals a paternal genome dosage effect on gene expression levels with strong enrichment for dysregulated abiotic stress-related genes in the paternal excess F1 triploids. This study demonstrates that heterosis can be triggered without allelic diversity in F1 triploid plants. Heterosis without heterozygosity in plants can be induced via an epigenetic “chromosome imprinting” like parental genome dosage effect requiring paternal transmission of an additional chromosome set 4 or 5 biological replicates per ploidy level, each replicate being a single two weeks old seedling
2014-08-01 | E-GEOD-52885 | biostudies-arrayexpress
Project description:Adult female Wistar rats (about 220g) obtained from a breeding colony were mated and fed either a protein sufficient (PS) or protein restricted (PR) diet (n = 6 per dietary group) during F0 pregnancy which provided an increase in energy of approximately 25% compared to the diet fed to the breeding colony (2018S). During lactation dams were fed AIN93G and litters were standardisied to 8 offspring within 24 hours of birth with a bias towards females. Offpsring were weaned onto AIN93M at postnatal day 28 and F1 and F2 females were mated on postnatal day 70 (n = 6 per F0 dietary group). F1 and F2 dams were fed the PS diet during pregnancy and AIN93G during lactation. Offspring were weaned onto AIN93M. On postnatal day 70 unmated female offspring were fasted for 12 hours then sacrificed for hepatic transcritpome analysis by microarray. Expression of 1,684 genes differed by at least 2 fold between adult female F1 offspring of F0 dams from both dietary groups. 1680 genes were altered in F2 offspring and 2,065 genes altered in F3 offspring. Expression of 113 genes was altered in all three generations. Of these, 47% showed directionally opposite differences between generations. Gene ontology analysis revealed clear differences in the pathways altered in each generation. F1 and F2 offspring of F0 dams fed a PR diet showed impaired fasting glucose homeostasis. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) expression was elevated in F1 and F2 offspring from F0 PR dams, but decreased in F3, compared to PS offspring
2011-06-01 | E-MEXP-3205 | biostudies-arrayexpress
Project description:Heterosis occurs where F1 offspring display superior characteristics to the parents. Heterosis is usually considered to result from crosses of genetically distinct (e.g. homozygous inbred) parents producing heterozygous F1 offspring. Most mechanistic models for heterosis require genetically heterozygous F1 hybrid offspring harbouring allelic diversity. Epigenetic or dosage models for heterosis could allow for heterosis effects in F1 offspring that display no allelic diversity with their parents. Reciprocal inter-ploidy crosses between diploid (2x) and tetraploid (4x) lines in the same genetic background generates genetically identical F1 triploids (3x). Such reciprocal F1 triploids differ according to whether the additional chromosome set is either maternally (maternal excess) or paternally inherited (paternal excess). Biomass accumulation and abiotic stress tolerance between the parental (2x and 4x) and reciprocal F1 triploid (3x) offspring of Arabidopsis thaliana accession C24 reveals a strong parental genome-dosage induced heterosis in the paternal-excess triploid F1 plants. In these F1 triploids, the circadian clock related genes CCA1 and TOC1, and the growth factors PIF4 and PIF5, display different expression levels compared to the non-heterotic maternal excess F1 triploid siblings. Whole transcriptome profiling reveals a paternal genome dosage effect on gene expression levels with strong enrichment for dysregulated abiotic stress-related genes in the paternal excess F1 triploids. This study demonstrates that heterosis can be triggered without allelic diversity in F1 triploid plants. Heterosis without heterozygosity in plants can be induced via an epigenetic “chromosome imprinting” like parental genome dosage effect requiring paternal transmission of an additional chromosome set
2014-08-01 | GSE52885 | GEO
Project description:Parental exposure to environmental stress can result in an increased diseases risk in the offspring. Although literature on maternal contribution to hereditary diseases are growing, the paternal contribution is frequently underrecognized. Since human studies reported that 80% of transmitted mutations arise in the paternal germline, it is crucial to understand the mechanism underlying the paternally inherited genome instability. Ionizing radiation (IR) is a major source of mutagenesis through inducing DNA double-strand breaks (DSBs). Here, we used sex-separated C. elegans mutants to investigate the paternal contribution to IR-induced transgenerational effects. Specifically, we found that paternal exposure to IR leads to a transgenerational embryonic lethality, and this effect is only observed when the radiation exposure occurred close to the time of fertilization. In the offspring of the irradiated males (F1 generation), we detected various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement, and aneuploidy. These phenotypes are attributed to the usage of two error-prone repair machinery, the polymerase-theta mediated end joining (TMEJ) and the non-homologous End Joining (NHEJ). Surprisingly, depletion of a human histone H1.0 ortholog, HIS-24, can significantly rescue this transgenerational embryonic lethality. Moreover, this rescue effect is associated with the downregulation of heterochromatin marker histone 3 lysine 9 di-methylation (H3K9me2), and the knocking-down of heterochromatin protein, HPL-1, could mimic the rescue effect of HIS-24 depletion. We also noticed that removal of the histone H1 and heterochromatin marker could activate the error-free repair machinery, Homologous Recombination repair (HR), thus improving the viability of the offspring carrying paternally inherited DNA damage. Altogether, our work sheds light on the importance of paternal radiation exposure on the health of offspring. In addition, our work establishes a previously unknown mechanism underlying the transgenerational genome instability and provides a potential therapeutic target for preventing the hereditary diseases caused by paternal radiation exposure.
2022-10-18 | PXD031873 | Pride