Maternal obesity alters methylation level of cytosine in CpG island for epigenetic inheritance in fetal umbilical cord blood

Abstract

Background Over the past few decades, global maternal obesity prevalence has rapidly increased. This condition may induce long-lasting pathophysiological effects on either fetal or infant health that could be attributable to unknown unique changes in the umbilical blood composition. Methods A total of 34 overweight/obese and 32 normal-weight pregnant women were recruited. Fifteen umbilical blood samples including 8 overweight/obese subjects and 7 normal weight women were sequenced using Targeted Bisulfite Sequencing technology to detect the average methylation level of cytosine and identify the differentially methylated region (DMR). GO and KEGG analyses were then employed to perform pathway enrichment analysis of DMR-related genes and promoters. Moreover, the mRNA levels of methylation-related genes histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) were characterized in the samples obtained from these two groups. Results Average methylated cytosine levels in both the CpG islands (CGI) and promoter significantly decreased in overweight/obese groups. A total of 1669 DMRs exhibited differences in their DNA methylation status between the overweight/obese and control groups. GO and KEGG analyses revealed that DMR-related genes and promoters were enriched in the metabolism, cancer and cardiomyopathy signaling pathways. Furthermore, the HDACs and DNMTs mRNA levels trended to decline in overweight/obese groups. Conclusions Decreased methylated cytosine levels in overweight/obese women induce the gene expression activity at a higher level than in the control group. DMRs between these two groups in the fetal blood may contribute to the changes in gene transcription that underlie the increased risk of metabolic disorders, cancers and cardiomyopathy in their offspring.

Gestational diabetes mellitus changes the DNA methylation profile in cord blood and leads to neonatal immune dysregulation

“…In general, low expression of DNMT1, DNMT3a and DNMT3b accelerates gene expression. However, DNMT1 and DNMT3b were signi cantly reduced in obese pregnant women [22]. Compared with GDM, the expression level in obese pregnant women decreased relatively less.…”

“…Umbilical cord blood testing monitors the fetus's health during development in the clinical setting [25]. However, detecting DNA methylation in the cord blood of GDM pregnant women is not ideal [17,22]. To improve this situation, this study reduced the in uence of other characteristics on the results at the sample collection level.…”

Immunity of turbot Induced by inactivated vaccine of Aeromonas salmonicida from the perspective of DNA methylation

“…This situation might be due to the distribution of many CpG islands (CGI) with high CpG sequence density in the promoter region. According to statistics, about 70% of vertebrate annotated gene promoters are related to CGI ( 23 , 24 ) and CG sites in CGI are generally in a non-methylated state, while CG sites located outside CGI are more easily modified by methylation, so the methylation level of promoter regions was significantly lower than that of other gene functional elements ( 25 ). When CGI undergo methylation modification, the methylation level of promoter region changes and generally accompanied by the inhibition of gene transcription, resulting in gene silencing ( 26 , 27 ).…”

Maternal obesity and placental function: impaired maternal–fetal axis

“…Moreover, gestational weight gain in pregnant women with obesity was associated with cord blood cell DNA methylation [ 109 ]. Average methylated cytosine levels in both the CpG islands and promoters were shown to be significantly decreased in cord blood from overweight and obese groups [ 110 ]. Importantly, a longitudinal birth cohort study, which was across a period from birth to 18 years, showed a significant connection between cord DNA methylation marks and postnatal BMI trajectories [ 111 ].…”