Abstract
Background Gestational weight gain (GWG) is one of the crucial factors affecting fetal growth as well as the in utero environment, influencing fetal cell programming during development. We reported previously that GWG affected the occurrence of outlying CpG methylation values of placental DNA in a U-shaped manner, with the occurrence of outlying values from adequate GWG subjects positioned at the bottom of the curve. In the present study, we aimed to elucidate the effects of GWG on the infant epigenome by the view that the influence of insufficient GWG on infant DNA methylation may turn in some other direction at the borderline of the optimal weight gain. Method We collected cord blood from 60 subjects with uncomplicated term delivery whose mean pre-pregnancy body mass index and mean GWG was 19.8 ± 1.9 and 8.1 ± 4.3 kg, respectively. Cord blood DNA was underwent analysis using the Infinium MethylationEPIC BeadChip to profile genome-wide methylation status. Results GWG was continuously associated with cord blood DNA methylation at five CpG loci significantly (multiple test corrected p-value, 0.043) in the lower than upper limit of the recommended GWG group (n = 51). The significant association between DNA methylation levels and GWG was disappeared when added 9 subjects who gained weight more than upper limit of recommendation during pregnancy. The methylation plot of the five loci plateaued or traced a U-curve near the border of the upper limit of the GWG recommendation. Cord blood DNA methylation of these five were all negatively associated with GWG. Validation using deep targeted bisulfite sequencing reproduced negative correlations between GWG and methylation levels within one of the five targets; at the upstream of LINC01816 . This region has been annotated as a promoter or an enhancer depending on blood cell types based on their epigenetic marks. Conclusions It is known that demethylation at enhancer region in genome is one of the features during late fetal development. We found that insufficient GWG showed higher methylation status in some enhancer-candidate loci in cord blood cells, which may indicate incomplete demethylation during in utero development.
DNA methylation signatures in cord blood associated with maternal gestational weight gain: results from the ALSPAC cohort
