Accelerated Placental Aging in Early Onset Preeclampsia Pregnancies Identified By DNA Methylation

Figures & data

Figure 1.  DNA methylation accurately predicts gestational age of the placenta.

The correlation between the chronological and DNA methylation gestational age of each placenta in the (A) training dataset and the (B) validation dataset. (C) A heatmap visualizing the gradual changes in DNA methylation in each of the 62 CpG sites (rows) across gestation in all samples (columns). The samples have been ordered by increasing gestational age and the probes have been ordered by the increasing magnitude of correlation with gestational age. The dataset heatmap represents the origin of each sample.

Figure 2.  Gestational age acceleration in early-onset preeclampsia.

Placentas from pregnancies complicated by early-onset PE (A) show a higher DNAm GA compared with their Chron GA. (B) Placentas from late-onset PE do not show any difference between the chronological and DNA methylation gestational age. Error bars are represented as standard deviations.

Chron GA: Chronological gestational age; DNAm GA: DNA methylation gestational age.

Table 1.  A description of the DNA methylation datasets containing placental tissue used in this study.

GEO accession	Dataset summary	Platform	Number of placental tissue samples	Gestational age range (weeks)
GSE31781	Placental tissue samples from three gestational age time points	27k	18 first trimester, 10 second trimester, 14 term	8–42
GSE36642	Cord blood and placentas from MZ and DZ twins	27k	28 third trimester	32–38
GSE36829	Placental tissue from term pregnancies	27k	48 term	37–42
GSE59274	Placental tissue samples from women with PE or uncomplicated pregnancies	27k	24 uncomplicated, 24 PE	28–41
GSE46573	Epigenome-wide association study	450k	2 term	NA
GSE52576	Genome-wide human imprinting analysis of different healthy human tissue	450k	4 term	NA
GSE54399	Whole cord blood and placental tissue from normal pregnancies	450k	24 uncomplicated	NA
GSE57767	Placental tissue samples from normal term, preterm PE and term PE women	450k	14 uncomplicated, 12 preterm PE, 19 term PE	NA
GSE44667	Placental tissue from women with EOPET and gestational age matched controls	450k	20 third trimester, 20 PE	25–37
GSE66210	First trimester chorionic villus samples from normal and trisomy pregnancies	450k	12 normal, 12 trisomy 21, 12 trisomy 18, 6 trisomy 13	NA
GSE73375	Placental tissue samples from preeclamptic and normotensive women	450k	17 uncomplicated, 19 PE	NA
GSE74738	Placental tissue from uncomplicated pregnancies	450k	28 term	36–42
This study	Placental tissue from uncomplicated elective cesarean pregnancies	27k	22 term	35–40

27k: Illumina Infinium Human Methylation27; 450k: Illumina Infinium HumanMethylation450; DZ: Dizygotic; EOPET: Early onset preeclampsia; GEO: Gene Expression Omnibus; MZ: Monozygotic; NA: Not available; PE: Preeclampsia.