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Effects of paternal methionine supplementation on sperm DNA methylation and embryo transcriptome in sheep

ABSTRACT: We examined how a prepubertal methionine-enriched paternal diet affected sperm DNA methylation and its subsequent effects on embryo gene expression.

ORGANISM(S): Ovis aries

PROVIDER: GSE215129 | GEO | 2023/02/10

REPOSITORIES: GEO

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Effects of paternal methionine supplementation on sperm DNA methylation and embryo transcriptome in sheep

Project description:Effects of paternal methionine supplementation on sperm DNA methylation and embryo transcriptome in sheep

| PRJNA888977 | ENA

Effects of paternal methionine supplementation on sperm DNA methylation and embryo transcriptome in sheep.

Project description:Environmental effects on gene expression and offspring development can be mediated by epigenetic modifications. It is well established that maternal diet influences DNA methylation patterns and phenotypes in the offspring; however, the epigenetic effects of paternal diet on developing offspring warrants further investigation. Here, we examined how a prepubertal methionine-enriched paternal diet affected sperm DNA methylation and its subsequent effects on embryo gene expression. Three treatment and three control rams were bred to seven ewes, and blastocysts were flushed for RNA extraction. Semen was collected from all rams and submitted for reduced representation bisulfite sequencing analysis. In total, 166 differentially methylated cytosines were identified in the sperm from treatment versus control rams. Nine genes were found to be differentially expressed in embryos produced from treatment versus control rams, and seven differentially methylated cytosines in the sperm were found to be highly correlated with gene expression in the embryos. Our results demonstrate that sperm methylation differences induced by diet may influence fetal programming.

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Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin

Project description:Sperm chromatin retains small amounts of histones, and the chromatin states of sperm mirror gene expression programs of the next generation. It remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here we developed a novel mouse model of paternal epigenetic inheritance in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology, we rescued infertility of mice absent of Polycomb protein SCML2, which is the regulator of germline gene expression through the establishment of H3K27me3 on bivalent promoters with other active marks H3K4me2/3. In F1 males of Scml2-knockout mice, which has wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in mature sperm. Thus, SCML2 mediates intergenerational inheritance of paternal epigenetic information through the regulation of sperm chromatin.

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Sperm DNA Methylation Epimutation Biomarker for Paternal Offspring Autism Susceptibility

Project description:Autism spectrum disorder (ASD) has increased over ten-fold over the past several decades, and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now thought to be an important factor. Epigenetic alterations, such as DNA methylation have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility. Sperm samples were obtained from fathers, many undergoing in vitro fertilization (IVF) procedures, that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. Differential DNA methylation regions (DMRs) were identified in the sperm of fathers with autistic children in comparison to those without ASD children. An MeDIP-seq procedure was used to identify DMRs. The genomic features and genes associated with the DMRs were identified. The potential sperm DMR biomarker was validated with a blinded test set of individuals. Observations demonstrate a significant set of DMRs in sperm can potentially act as a biomarker for paternal offspring autism susceptibility.

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Targeted reprogramming of H3K27me3 resets epigenetic memory in plant paternal chromatin [sperm]

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2020-03-17 | GSE144899 | GEO

Paternal chronic folate supplementation induced transgenerational inheritance of acquired developmental and metabolic changes in chickens

Project description:Increasing evidence indicates that the paternal diet can result in offspring metabolic changes. A proposed mechanism for paternal transmission of environmental information is via the sperm noncoding RNAs, but the definite mechanism remains unclear in birds.

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Project description:Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and -susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation. We demonstrate differences in offspring from stressed fathers that depend upon paternal category (resilient vs susceptible) and offspring sex. Importantly, artificial insemination reveals that sperm mediates some of the behavioral phenotypes seen in offspring. Using RNA-sequencing we report substantial and distinct changes in the transcriptomic profiles of sperm following CSDS in susceptible vs resilient fathers, with alterations in long noncoding RNAs (lncRNAs) predominating especially in susceptibility. Correlation analysis revealed that these alterations were accompanied by a loss of regulation of protein-coding genes by lncRNAs in sperm of susceptible males. We also identify several co-expression gene modules that are enriched in differentially expressed genes in sperm from either resilient or susceptible fathers. Taken together, these studies advance our understanding of intergenerational epigenetic transmission of behavioral experience.

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Targeted reprogramming of H3K27me3 resets epigenetic memory in plant paternal chromatin [sperm - third party reanalysis]

2020-03-17 | GSE144900 | GEO

Paternal exposure to Arctic contaminants alters the sperm epigenome and induces negative pregnancy outcomes transgenerationally

Project description:Paternal exposure to environmentally-relevant Arctic contaminants induces adverse health outcomes and alters the sperm methylome over three generations.

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Paternal diet induces transgenerational epigenetic inheritance of DNA methylation signatures and phenotypes in sheep model

Project description:We examined whether paternal diet from weaning to puberty induces sperm DNA methylation changes that can be transmitted to subsequent generations. Over 100 methylated cytosines environmentally altered in the F0 generation were inherited by the F1 and F2 generations. Furthermore, the F0 paternal diet was associated with growth and male fertility phenotypes in these generations. Differentially methylated genes also showed correlations with gene expression.

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