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Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE207326 | GEO | 2022/09/09

REPOSITORIES: GEO

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Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [RNA-seq]

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

Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [ChIP-seq]

2022-09-09 | GSE207325 | GEO

Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition

Project description:Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition

| PRJNA854824 | ENA

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.

| S-EPMC3863903 | biostudies-other

Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [ChIP-seq]

Project description:Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [ChIP-seq]

| PRJNA854826 | ENA

Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [RNA-seq]

Project description:Paternal obesity alters the sperm epigenome and and is associated with changes in the placental transcriptome and its cellular composition [RNA-seq]

| PRJNA854827 | ENA

Paternal TCDD Exposure Alters the Placental Epigenome

Project description:Preterm birth (PTB), spontaneous parturition prior to 37 weeks gestation, is the leading cause of neonatal mortality. We previously demonstrated that developmental exposure of male mice (F1 animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with reduced sperm quantity/quality in adulthood and their control mating partners frequently delivered preterm. Reproductive defects persisted in the F2 and F3 descendants and mating partners also exhibited an enhanced risk of spontaneous PTB. Reproductive changes in the F3 males, the first generation without direct TCDD exposure, suggest epigenetic alterations occurred in the male germline. Importantly, the sperm epigenome impacts development of the placenta, a tissue which is known to influence the timing of parturition. Therefore, we conducted an epigenetic microarray analysis of control and F1 male derived placentae obtained on E18.5 of pregnancy.

2018-05-07 | GSE111948 | GEO

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).

2013-11-06 | E-GEOD-51819 | biostudies-arrayexpress

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.

2013-11-02 | E-GEOD-52017 | biostudies-arrayexpress

Paternal TCDD Exposure Alters the Placental Epigenome

Project description:Paternal TCDD Exposure Alters the Placental Epigenome

| PRJNA438666 | ENA