Variation in placenta-specific genomic imprinting is associated with intrauterine growth restriction.
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PROVIDER: PRJNA495170 | ENA |
REPOSITORIES: ENA
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Project description:The placenta has a critical role in fetal growth, with many key functions regulated by genomic imprinting. With the recent description of polymorphic placenta-specific imprinting, the molecular mechanisms leading to this curious epigenetic phenomenon are unknown, as is their involvement in pregnancies complications. Profiling ubiquitous and placenta-specific imprinted differentially methylated regions (DMRs) exposed isolated aberrant methylation at ubiquitous DMRs as well as abundant hypomethylation at placenta-specific DMRs. Analysis of underlying chromatin at polymorphic placenta-specific imprinted DMRs revealed biallelic enrichment of histone H3K4 methylation, a modification normally mutually exclusive with DNA methylation. Furthermore, characterisation of expression in intrauterine growth restricted samples (IUGRs) uncovered coordinated deregulation of the GPR1AS1-ZDBF2-ADAM23 locus. Our results emphasize that methylation is less stable at placenta-specific imprints compared to their ubiquitous counterparts and that further work is required to determine if these differences are the IUGR cause or reflect unique adaption of the placenta epigenome to developmental stresses.
2019-02-05 | GSE120981 | GEO
Project description:Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in the postnatal life. However, the underlying mechanisms by which IUGR affects fetuses remain incompletely understood. Here, we applied high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on fetal liver.
2016-03-15 | PXD003524 | Pride
Project description:Placental insufficiency is implicated in the intrauterine infection-associated spontaneous preterm birth. Using a mouse model of LPS-induced intrauterine inflammation that leads to preterm delivery, RNA-seq study was performed in the placenta at gestational day 17 to assess the transcriptome changes.
2020-11-27 | GSE151728 | GEO
Project description:Transcriptional profiling to map the changes in placental function subsequent to maternal experimental UTI that result in intrauterine growth restriction. One condition experiment: 2 biological replicates of placenta from mice with maternal experimental UTI, 2 biological replicates of placenta from mice with sham UTI.
2011-09-09 | E-GEOD-32028 | biostudies-arrayexpress
Project description:In this study, we profiled the placental proteome of IUGR twins and normal cotwins from 6 monochorionic twin pairs with selective intrauterine growth restriction (sIUGR).
2022-07-15 | PXD035369 | iProX
Project description:The placenta is critical for mammalian embryonic development because the embryo’s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through the placenta. However, the molecular mechanisms underlying this amino acid supply are poorly understood. In this study, we focused on the system A amino acid transporters, Slc38a1/SNAT1, Slc38a2/SNAT2, and Slc38a4/SNAT4, which carry neutral, short-side-chain amino acids, to determine their involvement in placental or embryonic development. A triple-target CRISPR screen identified Slc38a4/SNAT4 as the critical amino acid transporter for placental development in mice. We established mouse lines from the CRISPR founders with large deletions in Slc38a4 and found that, consistent with the imprinted paternal expression of Slc38a4/SNAT4 in ther placenta, paternal knockout (KO), but not maternal KO, of Slc38a4/SNAT4 caused placental hypoplasia associated with reduced fetal weight. Immunostaining revealed that SNAT4 was widely expressed in differentiating cytotrophoblasts and maturing trophoblasts at the maternal–fetal interface. A blood metabolome analysis revealed that amino acid concentrations were globally reduced in Slc38a4/SNAT4 mutant embryos. These results indicated that, in mice, SNAT4-mediated amino acid transport plays a major role in both placental and embryonic development. Given that expression of Slc38a4 in placentas is conserved in other species, our Slc38a4/SNAT4 mutant mice could be a promising model for the analysis of placental defects leading to intrauterine growth restriction in mammals.
2019-08-23 | GSE136212 | GEO
Project description:Our knowledge of genomic imprinting in primates is lagging behand that of mice largely due to the difficulties of allelic analyses in outbred animals. To understand imprinting dynamics in primates, we profiled transcriptomes, DNA methylomes and H3K27me3 in uniparental monkey embryos. We further developed single-nucleotide polymorphisms (SNP)-free methods, TARSII and CARSII, to identify germline differentially methylated regions (DMRs) in somatic tissues. Our comprehensive analyses showed that allelic DNA methylation, but not H3K27me3, is a major mark that correlates with paternal-biasedly expressed genes (PEGs) in uniparental monkey embryos. Interestingly, primate germline DMRs are different from PEG-associated DMRs in early embryos and are enriched in placenta. Strikingly, most placenta-specific germline DMRs are lost in placenta of cloned monkey. Collectively, our study establishes SNP-free germline DMR identification methods, defines developmental imprinting dynamics in primates and demonstrates imprinting defects in cloned monkey placenta, which provides important clues for improving primate cloning.
2021-09-07 | GSE159347 | GEO
Project description:Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g. type 2 diabetes mellitus; T2DM), manifesting sometimes decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations. Our studies focused specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood, and utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to intrauterine growth restriction (IUGR), but that they are of a substantially lesser degree and involve many fewer loci than the epigenomic dysregulation observed in cancer. This is consistent with a comparable study of individuals born following maternal starvation during the Dutch famine. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Our results give some insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. Direct comparison of DNA methylation in 10 neonatal CD34+ samples isolated from umbilical cord blood belonging to two groups: IUGR (n=5) and their age-matched controls (n=5). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).
2010-02-17 | E-GEOD-17727 | biostudies-arrayexpress
Project description: Not available
| S-EPMC6471577 | biostudies-literature
Project description:Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic repression of imprinted genes is unclear. ‘Imprinting control regions’ (ICRs), however, are consistently marked by histone H3 K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET-domain protein G9a. We find that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression is unchanged at the domains analysed, in spite of a global loss of H3-K9 di-methylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is lost in the absence of G9, and this correlates with a loss of H3K9me2 and H3K9me3. These findings provide the first in vivo evidence for the involvement of a SET domain protein in imprinting and highlight the importance of histone lysine methylation rather than DNA methylation in the maintenance of imprinting in the trophoblast lineage. Keywords: genetic modification
2008-01-24 | GSE7674 | GEO