Effect of high fat diet versus low fat diet on histone distribution in sperm of male mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE72211 | GEO | 2015/08/20
SECONDARY ACCESSION(S): PRJNA293365
REPOSITORIES: GEO
Similar Datasets
Project description:Spermatozoa harbor a complex and environment sensitive pool of small non-coding RNAs (sncRNA)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. We used two distinct paradigms of preconception acute high fat diet to dissect epididymal vs testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs and their fragments (mt-tsRNA) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with BMI and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA-seq of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that alterations of mt-tsRNAs are downstream of mitochondrial dysfunction. Most importantly, single embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilisation and implied them in the control of early embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, for the first time in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
2024-04-03 | GSE239815 | GEO
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.
2015-12-31 | E-GEOD-75544 | biostudies-arrayexpress
Project description:To further investigate the effect of high-fat diet on m6A modified expression profiles of mouse sperm RNA, we used whole-genome microarray expression profiles as a discovery platform to identify differential m6A modified genes under high-fat diet exposure. Male mice were fed normal chow (C) or 60% high-fat diet (HFD) from 5 weeks to 15 weeks old, and then sperm were obtained for Arraystar m6A-mRNA&lncRNA Epitranscriptomic Microarray. Results showed that hyper-methylated mRNAs were involved in multiple biological processes, including the "reproductive process," "gamete generation," and "spermatogenesis".
2023-12-22 | GSE241195 | GEO
Project description:The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring White adipose tissue mRNA expression profiling of F2-female offspring from F0-founders fed either a chow or a chronic HFD challenged. Adult females were challenged or not a high-fat diet for 12 weeks. White adipose tissue was dissected at an endpoint experiment. Rats were subjected to 4 hours fasting prior to anesthesia with pentobarbital and tissue collection.
2017-01-01 | GSE65182 | GEO
Project description:In this study, we aimed to find out how the sperm tsRNA involved in paternal high-fat diet induced abnormal gluconeogenesis of F1 offspring, and explore the underlying molecular mechanism of its regulation.
2022-02-18 | GSE196881 | GEO
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5’ halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of “epigenetic carrier” that mediate intergenerational inheritance of acquired traits.
2015-12-31 | GSE75544 | GEO
Project description:The discovery of RNAs (e.g. mRNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function in delivering additional paternal information aside from solely providing the DNA1. Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2, 3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat diet (HFD)-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40nt RNA fractions that are induced by HFD. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNA-28S), which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
2018-03-06 | GSE97645 | GEO
Project description:Growing evidence point towards a strong contribution of paternal factors in placental health with implications in adult-onset complex disease risk. We have recently demonstrated that paternal diet-induced obesity alters sperm histone methylation and is associated with metabolic disturbances in the next generation. Diet-sensitive epigenetic regions in sperm were found at genes involved in trophectoderm and placental development, and corresponded to epigenetic and gene expression profiles in these tissues. We sought to investigate whether paternal diet-induced obesity before conception can alter the placental transcriptome, and whether differential gene expression corresponds with sperm obesity-associated epigenetic signatures. C57BL6/J males were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. They were then bred to control-fed C57BL6/J females to induce pregnancies and E14.5 placentas were collected. RNA-sequencing was performed (n=4 per group per sex) to detect sex-specific transcriptional changes associated with paternal diet. At necropsy, sperm was collected for chromatin immunoprecipitation followed by sequencing (ChIP-seq; n=3 per group) targeting histone H3 lysine 4 tri-methylation (H3K4me3) to detect obesity-induced changes in H3K4me3 enrichment. There were sex-specific differentially expressed genes in placentas with some overlapping with promoters showing obesity-associated sperm epimutations. A deconvolution analysis using single-cell RNA-seq data from mouse E14.5 placenta (Han et al., Cell, 2018) revealed significant differences in trophoblast subtype proportions in placentas derived from HFD sires. This study highlights a previously underappreciated role of the placenta at the origin of paternally-induced metabolic disturbances in offspring.
2022-09-09 | GSE207313 | GEO
Project description:Growing evidence point towards a strong contribution of paternal factors in placental health with implications in adult-onset complex disease risk. We have recently demonstrated that paternal diet-induced obesity alters sperm histone methylation and is associated with metabolic disturbances in the next generation. Diet-sensitive epigenetic regions in sperm were found at genes involved in trophectoderm and placental development, and corresponded to epigenetic and gene expression profiles in these tissues. We sought to investigate whether paternal diet-induced obesity before conception can alter the placental transcriptome, and whether differential gene expression corresponds with sperm obesity-associated epigenetic signatures. C57BL6/J males were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. They were then bred to control-fed C57BL6/J females to induce pregnancies and E14.5 placentas were collected. RNA-sequencing was performed (n=4 per group per sex) to detect sex-specific transcriptional changes associated with paternal diet. At necropsy, sperm was collected for chromatin immunoprecipitation followed by sequencing (ChIP-seq; n=3 per group) targeting histone H3 lysine 4 tri-methylation (H3K4me3) to detect obesity-induced changes in H3K4me3 enrichment. There were sex-specific differentially expressed genes in placentas with some overlapping with promoters showing obesity-associated sperm epimutations. A deconvolution analysis using single-cell RNA-seq data from mouse E14.5 placenta (Han et al., Cell, 2018) revealed significant differences in trophoblast subtype proportions in placentas derived from HFD sires. This study highlights a previously underappreciated role of the placenta at the origin of paternally-induced metabolic disturbances in offspring.
2022-09-09 | GSE207325 | GEO
Project description:Spermatozoa have a unique genome organization: their chromatin is almost completely devoid of histones and is formed instead of protamines which confer a high level of compaction and preserve paternal genome integrity until fertilization. Histone-to-protamine transition takes place in spermatids and is indispensable for the production of functional sperm. Here we show that the H3K79-methyltransferase DOT1L controls spermatid chromatin remodelling and subsequent reorganization and compaction of spermatozoon genome. Using a mouse model in which Dot1l is knocked-out (KO) in postnatal male germ cells, we found that Dot1l-KO sperm chromatin is less compact and has an abnormal content, characterized by the presence of transition proteins, immature protamine 2 forms and a higher level of histones. Proteomics and transcriptomics analyses performed on spermatids reveal that Dot1l-KO modifies the chromatin prior to histone removal, and leads to the deregulation of genes involved in flagellum formation and apoptosis during spermatid differentiation. As a consequence of these chromatin and gene expression defects, Dot1l-KO spermatozoa have less compact heads and are less motile, which results in impaired fertility.
2023-03-30 | PXD030734 | Pride