A number of studies have suggested that lifestyle factors during pregnancy, including diet and cigarette smoking, may influence the long term health of offspring. Whether maternal leisure-time physical activity (LTPA) during pregnancy might have a similar effect is unknown. One mechanism by which LTPA might influence offspring health is DNA methylation, where methyl groups are added to cytosine bases in DNA particularly at areas in the genome rich in cytosine and guanine bases (CpG islands). The purpose of this dissertation was to determine the relationship between maternal LTPA during pregnancy and offspring DNA methylation, both globally and in metabolism-related candidate genes, in infant blood spots.We used the Archive for Research on Child Health (ARCH) study data set, which has been ongoing at Michigan State University (MSU) since 2007. At enrollment, subjects completed questionnaires on demographic information as well as LTPA. We matched highly active subjects (averaged 637.5 minutes per week of moderate or vigorous physical activity (MVPA); n = 14) to low active subjects (averaged 60.4 minutes per week MVPA; n = 28) based on maternal age and race. Subjects were contacted via telephone to ask for consent to link physical activity data to their child's blood spot which was obtained at birth. Following DNA isolation and bisulfite treatment, we used pyrosequencing to determine methylation levels of long interspersed nucleotide elements (LINE-1) (global methylation) and PPARgamma;, PGC1-alpha;, IGF2, PDK4, and TCF7L2.We found no differences between high active and low active groups for LINE-1 methylation, an indicator of global methylation (Aim 1). For Aim 2, the only differences in candidate gene methylation between the two groups was at two CpG sites in the P2 promoter of IGF2; in both instances the low active group had significantly higher DNA methylation than the high active group (p = 0.020 and 0.047). However, the meaning of these differences is not clear. Also, mean methylation over eight P2 promoter sites for IGF2 was significantly higher in the low active group (p = 0.045), but there were no other differences in mean methylation levels for any candidate gene.Overall these results suggest no effect of maternal LTPA on global and candidate gene methylation profiles, with the exception of IGF2 methylation. This research is a unique pilot study of maternal LTPA in pregnancy and its effects on DNA methylation, in humans. Possible reasons for the mostly null findings include our choice of biologic sample (blood spots), lack of transfer of methylation profile from mother to offspring, measurement of methylation rather than gene expression, and inadequate LTPA stimulus. Future studies should include examination of the role of higher levels of maternal LTPA on both maternal and infant umbilical cord blood samples, and determination of the role of maternal LTPA on both DNA methylation and gene expression.
Read
