Early Pregnancy Maternal Blood DNA Methylation in Repeat Pregnancies and Change in Gestational Diabetes Mellitus Status—A Pilot Study

Abstract

Repeat pregnancies with different perinatal outcomes minimize underlying maternal genetic diversity and provide unique opportunities to investigate nongenetic risk factors and epigenetic mechanisms of pregnancy complications. We investigated gestational diabetes mellitus (GDM)-related differential DNA methylation in early pregnancy peripheral blood samples collected from women who had a change in GDM status in repeat pregnancies. Six study participants were randomly selected from among women who had 2 consecutive pregnancies, only 1 of which was complicated by GDM (case pregnancy) and the other was not (control pregnancy). Epigenome-wide DNA methylation was profiled using Illumina HumanMethylation 27 BeadChips. Differential Identification using Mixture Ensemble and false discovery rate (<10%) cutoffs were used to identify differentially methylated targets between the 2 pregnancies of each participant. Overall, 27 target sites, 17 hypomethylated (fold change [FC] range: 0.77-0.99) and 10 hypermethylated (FC range: 1.01-1.09), were differentially methylated between GDM and control pregnancies among 5 or more study participants. Novel genes were related to identified hypomethylated (such as NDUFC1, HAPLN3, HHLA3, and RHOG) or hypermethylated sites (such as SEP11, ZAR1, and DDR). Genes related to identified sites participated in cell morphology, cellular assembly, cellular organization, cellular compromise, and cell cycle. Our findings support early pregnancy peripheral blood DNA methylation differences in repeat pregnancies with change in GDM status. Similar, larger, and repeat pregnancy studies can enhance biomarker discovery and mechanistic studies of GDM.

Molecular Biomarkers for Gestational Diabetes Mellitus

“…The study showed that global DNA methylation was not associated with GDM in a South African population, suggesting that the method may be too crude to detect subtle glucose intolerance, and that gene-specific methylation is warranted in this population. Genome-wide DNA methylation profiling in maternal blood during GDM was conducted using methylation bead chip arrays [ 115 , 116 , 117 ]. Methylation bead chip arrays can interrogate between 27,000 and 850,000 CpG sites across the genome at a single-nucleotide resolution.…”

“…Methylation bead chip arrays can interrogate between 27,000 and 850,000 CpG sites across the genome at a single-nucleotide resolution. In one of the earliest studies using bead chip arrays, Enquobahrie et al reported that DNA methylation changes occurred early during pregnancy in six women with repeat pregnancies, one of which was complicated by GDM [ 116 ]. They reported that 17 CpG sites were hypomethylated and 10 CpG sites were hypermethylated between GDM and normal pregnancies within the same women.…”

Clinical Features of Babies Born to Mothers with Oligohydramnios: A Two Years’ Experience

“…Choline is an essential nutrient [ 42 – 47 ]. Both human studies and animal models suggest that choline intake during pregnancy has the potential to modify epigenetic states in the offspring with implications for adult health and later chronic disease risk [ 48 – 52 ]. We observed that dietary free and total choline intakes at entry were significantly lower in cases of preterm delivery ( Table 1 ).…”

The Effect Gestational Diabetes has on DNA Methylation as Related to Fetal Development and the Outcomes of the Mother and Offspring

“…placental cotyledon tissue [6,38], 2) Studies limited to cord blood [39][40][41], 3) Studies comparing cord blood and placental cotyledon tissue [42], 4) Studies involving cord blood and maternal blood of GDM mothers [43], and 5) Studies limited to maternal blood of GDM mothers [44]. Group 1 studies indicated that mothers with GDM had significantly higher degree of placental DNA methylation than control groups.…”