Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy.
Am J Respir Crit Care Med. 2017 Apr 19. Epub 2017 Apr 19. PMID: 28422514
Lyndsey E Shorey-Kendrick
BACKGROUND: Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We recently demonstrated in a randomized clinical trial (NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at one year of age.
OBJECTIVES: To determine if vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes.
METHODS: Targeted bisulfite sequencing was performed using a subset of placentas, cord bloods and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood DMRs using bisulfite amplicon sequencing.
RESULTS: The majority (69.03%) of CpGs with≥ 10% methylation difference between placebo and non-smoker groups were restored (by at least 50%) towards non-smoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs.
CONCLUSIONS: We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.