Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers. RNA from 8 Early Onset Preeclampsia placentas and 8 gestational age matched controls
Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers.
Project description:Preeclampsia is one of the leading causes of maternal death worldwide. While the root cause is still unknown, the underlying biology of the disorder is becoming more clear. We recently published a study showing large, significant differences in DNA methylation in 3rd trimester placental samples associated with early-onset preeclampsia (EOPET) compared to controls. In this study, to identify DNA methylation differences associated with preeclampsia that occur early in pregnancy and to further delineate common EOPET-associated differences, we utilized a genetic defect, trisomy 16 (T16), that is predisposing to preeclampsia. We ran T16 placental samples from the 1st trimester (n=5) and 3rd trimester (n=10) against gestational age matched controls on the Illumina Infinium HumanMethylation450 BeadChip. Third trimester samples were from pregnancies with T16 confined to the placenta (confined placental mosaicism 16;CPM16), and consisted of samples that were and were not associated with EOPET (n=5 each). We identified a large number of DNA methylation differences in CPM16 samples compared to controls using stringent criteria (n=2254;False Discovery Rate <0.01, ->0.15). Several of these differences (11%) overlapped differences observed in chromosomally normal EOPET using similarly stringent criteria (FDR<0.01;->0.125). Isolating EOPET-associated probes produced a similar - distribution amongst CPM16 samples, although samples associated with EOPET showed a tendency towards larger DNA methylation differences. We also identified 262 DNA methylation differences between 1st trimester T16 and 1st trimester controls. Of these, 77 overlapped differences seen in 3rd trimester CPM16. Investigating these 77 T16/CPM16 specific DNA methylation differences, we identified three probes near two genes (ARGHEF37 and JUNB) that were also present as EOPET-associated methylation differences. In summary, we identified significant overlapping DNA methylation profiles of placentas with T16 and chromosomally normal placentas associated with EOPET. Specific DNA methylation marks within these profiles may be of future clinical utility in early identification of pregnancies susceptible to EOPET.
Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers.
Project description:Preeclampsia and intrauterine growth restriction (IUGR) are two of the most common adverse pregnancy outcomes, but their underlying causes are mostly unknown. Although multiple studies have investigated gene expression changes in these disorders, few studies have examined epigenetic changes. Analysis of the DNA methylation pattern associated with such pregnancies provides an alternative approach to identifying cellular changes involved in these disorders. We analyzed methylation of 1505 CpG sites associated with 807 genes in 26 placentas from early-onset preeclampsia (EOPET), late-onset preeclampsia, IUGR and control subjects using an Illumina GoldenGate Methylation panel. Thirty-four loci were hypomethylated (false discovery rate <10% and methylation difference >10%) in the early-onset preeclamptic placentas while no and only five differentially methylated loci were found in late-onset preeclamptic and IUGR placentas, respectively. Hypomethylation of 4 loci in EOPET was further confirmed by bisulfite pyrosequencing of 26 independent placental samples. The promoter of TIMP3 was confirmed to be significantly hypomethylated in EOPET placentas (P=0.00001). Our results suggest that gene-specific hypomethylation may be a common phenomenon in EOPET placentas, and that TIMP3 could serve as a potential prenatal diagnostic marker for EOPET.
Project description:Preeclampsia is one of the leading causes of maternal death worldwide. While the root cause is still unknown, the underlying biology of the disorder is becoming more clear. We recently published a study showing large, significant differences in DNA methylation in 3rd trimester placental samples associated with early-onset preeclampsia (EOPET) compared to controls. In this study, to identify DNA methylation differences associated with preeclampsia that occur early in pregnancy and to further delineate common EOPET-associated differences, we utilized a genetic defect, trisomy 16 (T16), that is predisposing to preeclampsia. We ran T16 placental samples from the 1st trimester (n=5) and 3rd trimester (n=10) against gestational age matched controls on the Illumina Infinium HumanMethylation450 BeadChip. Third trimester samples were from pregnancies with T16 confined to the placenta (confined placental mosaicism 16;CPM16), and consisted of samples that were and were not associated with EOPET (n=5 each). We identified a large number of DNA methylation differences in CPM16 samples compared to controls using stringent criteria (n=2254;False Discovery Rate <0.01, ->0.15). Several of these differences (11%) overlapped differences observed in chromosomally normal EOPET using similarly stringent criteria (FDR<0.01;->0.125). Isolating EOPET-associated probes produced a similar - distribution amongst CPM16 samples, although samples associated with EOPET showed a tendency towards larger DNA methylation differences. We also identified 262 DNA methylation differences between 1st trimester T16 and 1st trimester controls. Of these, 77 overlapped differences seen in 3rd trimester CPM16. Investigating these 77 T16/CPM16 specific DNA methylation differences, we identified three probes near two genes (ARGHEF37 and JUNB) that were also present as EOPET-associated methylation differences. In summary, we identified significant overlapping DNA methylation profiles of placentas with T16 and chromosomally normal placentas associated with EOPET. Specific DNA methylation marks within these profiles may be of future clinical utility in early identification of pregnancies susceptible to EOPET. Bisulfite converted DNA from 5 1st trimester trisomy 16 placentas, 5 chromosomally normal 1st trimester placentas, 10 third trimester placentas from confined placental mosaicism placentas and 10 chromosomally normal 3rd trimester placentas