Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CpG Island methylation variation in placentae of Intra-Uterine Growth Restricted (IUGR) fetuses versus controls

ABSTRACT: Methylation profiling of CpG Island Methylation of genomic DNA samples extracted from placentae of Intra-Uterine Growth Restricted newborns and gestational age matched controls. These data can be used for methylation comparisons between these two types of samples. The results of such comparisons can be used to generate hypotheses on the involvement of DNA methylation variation in placenta development and fetal growth. Two-condition Methyl DNA Immunoprecipitation (MeDIP) experiment, IUGR vs. Control placenta samples. Biological replicates: 8 control, 8 IUGR cases.

ORGANISM(S): Homo sapiens

SUBMITTER: Rosanna Weksberg

PROVIDER: E-GEOD-22326 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

WNT2 promoter methylation in human placenta is associated with low birthweight percentile in the neonate.

Ferreira Jose C JC Choufani Sanaa S Grafodatskaya Daria D Butcher Darci T DT Zhao Chunhua C Chitayat David D Shuman Cheryl C Kingdom John J Keating Sarah S Weksberg Rosanna R

Epigenetics 20110401 4

Neonates with birthweights below the tenth percentile for gestational age are considered small for gestational age (SGA). Such infants have an increased risk for perinatal mortality and morbidity as well as an increased lifetime risk for adult onset disorders. Low birth weight percentile is etiologically heterogeneous and may result from maternal, fetal, placental and environmental factors. However, the molecular determinants of human SGA are not well elucidated. We proposed that fetal growth po ...[more]

PMID: 21474991

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Project description:Intrauterine growth restriction (IUGR) increases susceptibility to age-related diseases including type 2 diabetes (T2DM), and is associated with permanent and progressive changes in gene expression and epigenetic regulation. We studied cytosine methylation throughout the genome in pancreatic islets from a rat model of uteroplacental insufficiency, providing a novel and detailed assessment of the genomic distribution and locus-specific patterns of DNA methylation in normal islets as well as the changes that occur as a consequence of IUGR. Utilizing a high throughput approach to study DNA methylation at almost 1 million unique sites throughout the genome, we found ~1,400 changes in methylation (IUGR compared to control) with an estimated false discovery rate of 4.2%. These epigenetic differences were observed in IUGR male rats at 7 weeks of age, preceding the development of diabetes in this model. Therefore, these epigenetic differences represent candidates for mediating the pathogenesis of metabolic disease that occurs later in life in these animals. Moreover, many of the changes we identify are located near genes that regulate processes known to be abnormal in IUGR islets, such as vascularization, Î²-cell proliferation, insulin secretion, and cell death. Consistent changes in mRNA expression were identified at some of the epigenetically-dysregulated genes including Fgfr1, Gch1, Pcsk5, and Vgf. Globally, epigenetic dysregulation occurred preferentially at conserved intergenic sequences, which are candidate cis-regulatory elements driving differential expression of nearby genes. These results provide insights into the complex developmental consequences of IUGR, and suggest that changes in DNA methylation could mediate a constellation of changes in both gene expression and pancreatic islet development and function, with relevance to T2DM. Direct comparison of DNA methylation in 8 samples consisting of isolated, pooled pancreatic islets from 7-week-old male offspring belonging to 4 IUGR and 4 control litters (Sprague-Dawley rats). 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).

Project description:The maternal and paternal copies of the genome are both required for mammalian development and this is primarily due to imprinted genes, those that are mono-allelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilisation. There are a large number of germline DMRs that have not yet been associated with imprinting and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs, specifically in the human placenta, and investigated the dynamics of imprinted DMRs during development in somatic and extra-embryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 116 human tissue samples, publically available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. 43 known and 101 novel imprinted DMRs were identified in the human placenta, by comparing methylation between diandric and digynic triploids and female and male gametes. 72 novel DMRs showed a pattern consistent with placental-specific imprinting and this mono-allelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation specifically in placenta. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation For the identification of imprinted DMRs in the placenta, chorionic villous samples from 5 diandric and 5 digynic triploids pregnancies were assayed, along with a pooled sample of complete hydatiform moles (CHM). Placental chorionic villous samples (n=63) included 29 control pregnancies delivered at term, while the remaining 34 were delivered preterm or miscarried, or had abnormal MSS results, IUGR or LOPET. The preterm births were associated with one or more of: preterm labour, premature rupture of membranes (PROM), chorioamnionitis, placental abruption, and incompetent cervix. All samples were determined to be chromosomally normal using standard karyotyping or comparative genome hybridization, as previously described (Robinson et al. 2010). Two to four independent sites were taken from each placenta and after DNA extraction from chorionic villous, the DNA was pooled before being utilized in this study. Thirty-three fetal tissues, including brain (n=8), spinal cord (n=7), muscle (n=9), and kidney (n=9) were collected from second trimester foetuses, as previously described (Price et al. 2012). Adult female whole blood samples (n=10) were collected from control women. Extra-embryonic cell types (n=19), including cord blood (embryonic), cord, amniotic membrane, chorionic membrane, 1st, 2nd and 3rd trimester trophoblast and mesenchyme, and decidua (maternal), were isolated from control placental samples.

Dataset Information

CpG Island methylation variation in placentae of Intra-Uterine Growth Restricted (IUGR) fetuses versus controls

Publications

WNT2 promoter methylation in human placenta is associated with low birthweight percentile in the neonate.

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