Roman C, Dafashy T, Hegde S, Ashimi O and Bytautiene E
We searched OVID, PubMed and Web of Science, using MSH terms related to epigenetic changes, placenta, and preeclampsia, limiting the results to humans, English language, non-review articles, and publications between 2004 to 2014. 51 out of 207 studies met selection criteria for full data extraction. Array and profiling studies were included only if their results were validated by other methods. Next, 23 of 42 articles satisfied methodological quality criteria, including gestational age-matching and/or controlling or adjusting for confounders. Then, studies with a total score <10 out of 15 quality assessment points were excluded. MicroRNAs and genes resulting from review were investigated for interactions using Ingenuity Pathways Analysis.
Ten studies met the inclusion criteria for our review: 3 concerning DNA methylation and 7 studies regarding miRNA. There were no studies on histone modification by acetylation. Seventeen differentially regulated miRNAs were identified, with three reported in two studies. Nine miRNAs were upregulated, six downregulated, one was either upregulated or downregulated depending on the severity of preeclampsia, and one had conflicting results. Our review observed nine genes that were hypomethylated, one hypermethylated, while one was found not different between groups.
IPA’s microRNA analysis revealed that 16 miRNA from our list could be targeting 8,005 mRNAs. miRNAs were associated with 3 networks and 1 toxicity phenotype, hypomethylated genes with 2 networks and 5 toxicity, and one hypermethylated gene was not associated with any networks, while its toxicity list included regulation of mitochondria and renal necrosis. The common toxicity phenotype within upregulated miRNAs, downregulated miRNAs, and hypermethylated genes was associated with regulation of mitochondria.
Our review spotlights the gaps in knowledge about histone modifications associated with the preeclamptic placenta, emphasizes the importance of verifying the array results by other methods, and stresses the need to meticulously design future studies to included comparable samples groups.