Paternal exposure to Arctic contaminants alters the sperm epigenome and induces negative pregnancy outcomes transgenerationally
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE109056 | GEO | 2018/08/30
REPOSITORIES: GEO
Similar Datasets
Project description:Paternal exposure to Arctic contaminants alters the sperm epigenome and induces negative pregnancy outcomes transgenerationally
| PRJNA429491 | ENA
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.
| S-EPMC8594730 | biostudies-literature
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).
2013-11-06 | E-GEOD-51819 | biostudies-arrayexpress
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 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.
2013-11-02 | E-GEOD-52017 | biostudies-arrayexpress
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.
2013-11-06 | GSE51819 | GEO
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 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.
2013-11-02 | GSE52017 | GEO
Project description:The objective of this study was to identify the different functional genes involved in key biogeochemical cycles in the low Arctic regions. Understanding the microbial diversity in the Arctic region is an important step to determine the effects of climate change on these areas.
2021-03-11 | GSE168623 | GEO
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.
| S-EPMC3863903 | biostudies-other
Project description:C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, is primarily expressed on cells of the myeloid lineage, and to a lesser extent on endothelial cells and neurons in brain. Previous work demonstrated C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in Alzheimer Disease (AD) mouse models. In the Arctic AD mouse model, genetic deletion of C5aR1 prevented behavior deficits at 10 months. However, the molecular mechanisms of this protection has not been definitively demonstrated. To understand the role of microglial C5aR1 in the Arctic AD mouse model, we have taken advantage of the CX3CR1GFP and CCR2RFP reporter mice to distinguish microglia as GFP-positive and infiltrating monocytes as GFP and RFP positive, for subsequent transcriptome analysis on specifically sorted myeloid populations from wild type and AD mouse models. Immunohistochemical analysis of mice aged to 2, 5, 7 and 10 months showed no change in amyloid beta (Ab) deposition in the Arctic C5aR1 knockout (KO) mice relative to that seen in the Arctic mice. Of importance, no CCR2+ monocytes/macrophages were found near the plaques in the Arctic brain with or without C5aR1. RNA-seq analysis on microglia from these mice identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wildtype and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal proteins and protein degradation pathways that were increased in the Arctic mice were further increased in the Arctic/C5aR1KO mice. These data are consistent with a microglial polarization state with restricted induction of inflammatory genes and enhancement of clearance pathways.
2017-10-10 | GSE93824 | GEO
Project description:SCOPE:The effectiveness of maternal folate in reducing the risk of congenital malformations during pregnancy is well established. However, the role of the paternal folate status is scarcely investigated. The aim of this study is to investigate the evidence of associations between the paternal folate status and sperm quality, sperm epigenome, and pregnancy outcomes. METHODS AND RESULTS:Databases are searched up to December 2017 resulting in 3682 articles, of which 23 are retrieved for full-text assessment. Four out of thirteen human and two out of four animal studies show positive associations between folate concentrations and sperm parameters. An additional meta-analysis of four randomized controlled trials in subfertile men shows that the sperm concentration increases (3.54 95% confidence interval (CI) [-1.40 to 8.48]) after 3-6 months of 5 mg folic acid use per day compared to controls. Moreover, two out of two animal and one out of three human studies show significant alterations in the overall methylation of the sperm epigenome. One animal and one human study show associations between low folate intake and an increased risk of congenital malformations. CONCLUSIONS:This systematic review and meta-analysis shows evidence of associations between paternal folate status and sperm quality, fertility, congenital malformations, and placental weight.
| S-EPMC7317557 | biostudies-literature