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Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

ABSTRACT: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age.Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays.We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preeclampsia cases, but not term preeclampsia, compared with their chronological age. Therefore, early onset preeclampsia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.

SUBMITTER: Mayne BT

PROVIDER: S-EPMC6040051 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Mayne Benjamin T BT Leemaqz Shalem Y SY Smith Alicia K AK Breen James J Roberts Claire T CT Bianco-Miotto Tina T

Epigenomics 20161129 3

<h4>Aim</h4>To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age.<h4>Materials & methods</h4>Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays.<h4>Results & conclusion</h4>We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from ear ...[more]

PMID: 27894195

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Project description:IntroductionThe pathophysiology of preeclampsia is largely unknown. Serum placental induced growth factor (PlGF) levels are decreased during second trimester pregnancy. Aberrant DNA methylation is suggested to be involved in the etiology of preeclampsia (PE). We hypothesize that DNA methylation is altered in PE placentas determined the methylation index by measuring placental S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels. In addition, we assessed global DNA methylation status by long-interspersed nuclear element-1 (LINE-1) and DNA methylation status of the PlGF gene.MethodsPlacental tissue of 11 early onset PE (EOPE), 11 late onset PE (LOPE) and 60 controls consisting of 25 uncomplicated controls 20 fetal growth restriction (FGR) and 15 preterm births (PTB) controls was collected from a nested case-control study of The Rotterdam Periconceptional Cohort. RNA and DNA was isolated from placental tissue and DNA was treated with sodium bisulfite. SAM and SAH levels were measured by LC-ESI-MS/MS. Methylation of LINE-1 and PlGF genes was analyzed by Sequenom Epityper and. mRNA expression of PlGF was assessed with qPCR. Differences were assessed by analysis of covariance (ANCOVA) corrected for gestational age and birth weight.ResultsPlacental SAM levels were significantly lower in placental tissue of EOPE pregnancies compared to PTB controls (mean difference -240 ± 71.4 nmol/g protein, P = 0.01). PlGF DNA methylation was decreased in placental tissue of EOPE cases versus LOPE (mean difference -17.4 ± 5.1%, P = 0.01), uncomplicated controls (mean difference -23.4 ± 5.4%%, P <0.001), FGR controls (mean difference -17.9 ± 4.6%, P = 0.002) and PTB controls (mean difference -11.3 ± 3.8% P = 0.04). No significant differences were observed in SAH, SAM:SAH ratio, LINE-1 DNA methylation and PlGF mRNA expression between groups.DiscussionThe hypomethylation state of the placenta in EOPE, which is reflected by lower SAM and PlGF DNA hypomethylation underlines the possible role of placental DNA hypomethylation in the pathophysiology of EOPE, which needs further investigation.

Dataset Information

Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Publications

Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

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