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

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

PROVIDER: PRJNA429491 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6459580_1.fastq.gz	Fastqsanger.gz
	SRR6459580_2.fastq.gz	Fastqsanger.gz
	SRR6459590_1.fastq.gz	Fastqsanger.gz
	SRR6459590_2.fastq.gz	Fastqsanger.gz
	SRR6459600_1.fastq.gz	Fastqsanger.gz

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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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Low paternal dietary folate alters the sperm epigenome and is associated with negative pregnancy outcomes

Project description:Epidemiological studies suggest that a fatherâ€™s diet can influence offspring health. A proposed mechanism for paternal transmission of environmental information is via the sperm epigenome. The epigenome includes heritable information such as DNA methylation. We hypothesized that the dietary supply of methyl donors would alter epigenetic reprogramming in sperm. This hypothesis was examined by feeding male mice a folate deficient (FD) and folate sufficient (FS) diets and then generating and analyzing DNA methylation profiles of their sperm. C57BL/6 males were fed either the FS or FD diet throughout life (FS, n=32; FD, n=35; 2-3 month old). Pooled gene promoter DNA methylation profiles were generated from the sperm of three FS males and four FD males using the method of MeDIP (Methylated DNA Immunoprecipitation) followed by microarray hybridization.

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Disruption of histone methylation in developing sperm impairs offspring health transgenerationally [sperm]

Project description:A father’s lifetime experiences can be transmitted to his offspring to affect health and development. The mechanisms underlying paternal epigenetic transmission are unclear. Unlike somatic cells, there are few nucleosomes in sperm and their function in epigenetic inheritance is unknown. We generated transgenic mice in which overexpression of the histone H3 lysine 4 (H3K4) demethylase LSD1/KDM1A during spermatogenesis reduced H3K4 dimethylation in sperm. KDM1A overexpression in one generation severely impaired development and survivability of offspring. These defects persisted transgenerationally in the absence of KDM1A germ line expression and were associated with altered RNA profiles in sperm and offspring. We show that epigenetic inheritance of aberrant development can be initiated by histone demethylase activity in developing sperm, without changes to DNA methylation at CpG-rich regions.

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Low paternal dietary folate alters the sperm epigenome and is associated with negative pregnancy outcomes

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Disruption of histone methylation in developing sperm impairs offspring health transgenerationally [embryo]

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Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage.

Project description:Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated. We used a rat model to test the hypothesis that exposure to POPs during gestation and suckling leads to developmental defects that are transmitted to subsequent generations via the male lineage. Indeed, developmental exposure to an environmentally relevant Arctic POPs mixture impaired sperm quality and pregnancy outcomes across two subsequent, unexposed generations and altered sperm DNA methylation, some of which are also observed for two additional generations. Genes corresponding to the altered sperm methylome correspond to health problems encountered in the Inuit population. These findings demonstrate that the paternal methylome is sensitive to the environment and that some perturbations persist for at least two subsequent generations. In conclusion, although many factors influence health, paternal exposure to contaminants plays a heretofore-underappreciated role with sperm DNA methylation contributing to the molecular underpinnings involved.

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Low paternal dietary folate alters the sperm epigenome and is associated with negative pregnancy outcomes

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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Sperm-inherited H3K27me3 epialleles are transmitted transgenerationally in cis

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Low paternal dietary folate alters the sperm epigenome and is associated with negative pregnancy outcomes

2013-11-06 | GSE51819 | GEO

Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes.

Project description:Epidemiological studies suggest that a father's diet can influence offspring health. A proposed mechanism for paternal transmission of environmental information is via the sperm epigenome. The epigenome includes heritable information such as DNA methylation. We hypothesize that the dietary supply of methyl donors will alter epigenetic reprogramming in sperm. Here we feed male mice either a folate-deficient or folate-sufficient diet throughout life. Paternal folate deficiency is associated with increased birth defects in the offspring, which include craniofacial and musculoskeletal malformations. Genome-wide DNA methylation analysis and the subsequent functional analysis identify differential methylation in sperm of genes implicated in development, chronic diseases such as cancer, diabetes, autism and schizophrenia. While >300 genes are differentially expressed in offspring placenta, only two correspond to genes with differential methylation in sperm. This model suggests epigenetic transmission may involve sperm histone H3 methylation or DNA methylation and that adequate paternal dietary folate is essential for offspring health.

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