Differential placental methylation in preeclampsia, preterm and term pregnancies

Placenta. 2020 Apr:93:56-63. doi: 10.1016/j.placenta.2020.02.009. Epub 2020 Feb 11.

Abstract

Introduction: Preeclampsia (PE) is one of the leading causes of maternal mortality and morbidity worldwide. Recently, the role of epigenetic modifications in preeclampsia has been a focus of research. This study was to identified genes or pathways that may be associated with PE, and discuss whether the changes in the methylation level of these genes is related to the pathogenesis of PE.

Methods: The methylation levels of placental tissues between PE (n = 4), preterm birth (PB, n = 4) and term birth (TB, n = 4) were detected by Illumina Infinium HumanMethylation850 K BeadChip. Pyrosequencing and qRT-PCR were used to validated the methylation and expression levels of the genes with the most significant differences.

Results: The global methylation levels of placenta tissues in PE and PB were both higher compared to TB. After eliminated the effect of gestational age, there were 808 gene probes differentially methylated in PE compared to PB. We found 137 genes with 130 genes hypermethylated and 7 genes hypomethylated. CMIP, BLCAP and MICA genes were with the most significant differential methylation. The expression level of CMIP and BLCAP were both negatively correlated to the methylation levels, while the expression level of MICA was not related to its methylation levels.

Conclusion: The methylation levels in placenta tissues were associated with gestational ages. We indicated the expression levels of the significantly methylated genes were negatively correlated with the methylation levels, further functional researches were still needed to find out whether they are associated with the onset of preeclampsia.

Keywords: DNA methylation; Epigenetics; Placenta; Preeclampsia; Preterm birth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Case-Control Studies
  • CpG Islands / genetics
  • DNA Methylation*
  • Female
  • Gene Expression Profiling
  • Gestational Age
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Infant, Newborn
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Placenta / metabolism*
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Pregnancy Trimester, Third / genetics
  • Pregnancy Trimester, Third / metabolism
  • Premature Birth / genetics*
  • Premature Birth / metabolism
  • Premature Birth / pathology
  • Term Birth / genetics*
  • Term Birth / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • BLCAP protein, human
  • CMIP protein, human
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • Neoplasm Proteins