Unknown,Transcriptomics,Genomics,Proteomics

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Human IUGR placentas

ABSTRACT: IUGR (Intra-Uterine Growth Restriction) refers to a condition where the foetus does not reach its growth potential in utero. It is supposed to be often linked with placental dysfunction, especially of vascular origin. In this study, 4 pools of three placentas from human normal pregnancies and 4 pools of three placentas from IUGR human pregnancies, obtained after caesarean section near normal term , were used to prepare RNA. The cDNAs prepared from these RNA were hybridized to a Nimblegen expression array in order to detect differences in gene expression between normal and pathological placentas.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Vaiman

PROVIDER: E-MTAB-1956 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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).

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Human IUGR placentas

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