Associations between maternal prenatal stress, methylation changes in IGF1 and IGF2, and birth weight

Abstract

Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1. There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total of 24 mother-newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2.

Tracing human stem cell lineage during development using DNA methylation

“…As a previous publication (Morin et al 2017) had interrogated the potential of maternal blood contamination using these datasets we evaluated if any of the samples showed evident maternal blood contamination. Using a combination of the 10 CpGs reported by Morin et al and the calculation of DNA methylation age, we found one cord blood sample in the paired maternal-newborn GSE54399 dataset (Montoya-Williams et al 2017) was mostly maternal blood (DNA methylation age 44.5 years corresponding to the paired 45 years in the maternal sample and an adult hypermethylated pattern using the 10 markers of Morin et al (Morin et al 2017)). After removing this sample, we applied our FCO signature to these data and assessed how well it classified fetal from adult tissues by computing the area under the receiver operating characteristic curve (AUROC).…”

DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes

“…In total, we used data from 718 unrelated subjects from the general population without clinically obvious neurodevelopmental phenotypes, who had DNA extracted from peripheral blood and had undergone profiling with the Illumina 450k array (GEO: GSE54670 , GSE54399 , GSE51245 , GSE89353 , GSE36064 , GSE128801 , GSE53045 , GSE40279 , GSE42861 ). 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 We restricted subjects to those age <50 years to match our WS cohort and excluded one control sample, as it presented as outlier based on principal component analysis (PCA) of autosomal probes. For detailed information see Table S7 and Figure S5 .…”

Stress and the HPA Axis: Balancing Homeostasis and Fertility

“…Genome-wide analysis revealed several regions of DNA which were differentially methylated in offspring born from mothers of the Dutch famine, including genes related to growth and metabolism, which may contribute to the phenotypes reported [ 99 ]. In a separate study, differential methylation of IGF-1 in response to stress was associated with low birth weight in an African population [ 100 ]. Women who were directly exposed to the World Trade Center collapse in 2001 (either by being present or near the building while pregnant) and developed post-traumatic stress disorder (PTSD) gave birth to offspring that had lower birth weight and cortisol concentrations than offspring who were not exposed to maternal PTSD [ 101 , 102 ].…”