Cell-free DNA methylation profiling in early-onset preeclampsia using methylated DNA sequencing.

Area of Science:

• Epigenetics
• Genomics
• Maternal-fetal medicine

Background:

• Early-onset preeclampsia (EOPE) is associated with distinct DNA methylation profiles in maternal plasma cell-free DNA (cfDNA).
• Previous studies show inconsistent findings, and the biological mechanisms driving these methylation differences remain unclear.
• Understanding these mechanisms is crucial for improving EOPE diagnosis and management.

Purpose of the Study:

• To identify differentially methylated regions (DMRs) associated with EOPE in cfDNA.
• To investigate changes in tissue-specific cfDNA contributions in EOPE.
• To validate previously reported EOPE-associated methylation regions.

Main Methods:

• Collected cfDNA from EOPE pregnancies and controls in the first trimester and after diagnosis.
• Analyzed placental tissues from EOPE and control pregnancies using MeD-seq assays.
• Compared cfDNA concentration, placental contribution, and tissue-specific methylation patterns (liver, kidney, endothelium) between groups.

Main Results:

• Identified 249 DMRs in cfDNA after EOPE diagnosis and 606 DMRs in EOPE placentas.
• Observed a 20-fold increase in cfDNA concentration after EOPE diagnosis.
• Found decreased placental, liver, and kidney contributions but increased endothelium-specific methylation in cfDNA of EOPE cases.

Conclusions:

• Differential tissue contributions to cfDNA, especially from the endothelium, are likely responsible for observed DMRs in EOPE.
• Further research is needed to pinpoint the exact tissue origins of cfDNA DMRs in EOPE.
• Methodological heterogeneity may explain the lack of concordance across previous studies.