Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia

Area of Science:

• Reproductive Biology
• Genetics
• Epigenetics

Background:

• Maternal preeclampsia is linked to early placental development changes.
• Confined placental trisomy 16 mosaicism (CPM16) is a genetic placental abnormality strongly associated with preeclampsia.
• Previous research identified DNA methylation alterations in third-trimester placentae from early-onset preeclampsia (EOPET).

Purpose of the Study:

• To investigate if CPM16 exhibits similar DNA methylation alterations as observed in EOPET.
• To explore CPM16 as a potential model for studying EOPET-associated placental changes early in pregnancy.

Main Methods:

• Utilized the Illumina Infinium HumanMethylation450 BeadChip array.
• Compared third-trimester CPM16 placental samples (N=10) with gestational age-matched controls.
• Compared third-trimester CPM16 placentae with first-trimester trisomy 16 placentae (N=5).

Main Results:

• Identified 2254 differentially methylated CpGs in CPM16 placentae (FDR < 0.01, Δβ > 0.15).
• 11% of these CpGs overlapped with those found in chromosomally normal EOPET placentae (FDR < 0.01, Δβ > 0.125).
• The majority of EOPET-associated CpGs were significantly altered in CPM16, with shared changes near ARGHEF37 and JUNB also observed in first-trimester trisomy 16 placentae.

Conclusions:

• Widespread DNA methylation changes occur in trisomy 16 placentae, overlapping with changes seen in EOPET.
• CPM16 serves as a potential model for studying the progression of placental epigenetic alterations in EOPET throughout gestation.