Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy
| Autor: | Byung Park, Kristin Milner, Eliot R. Spindel, Lyndsey E. Shorey-Kendrick, Lina Gao, Brittany Vuylsteke, Cynthia D. Morris, Cindy T. McEvoy, Julja Burchard, Betsy Ferguson |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Lung Diseases 0301 basic medicine Pulmonary and Respiratory Medicine medicine.medical_specialty Offspring Bisulfite sequencing Physiology Ascorbic Acid Critical Care and Intensive Care Medicine Infant Newborn Diseases Pulmonary function testing 03 medical and health sciences Pregnancy Placenta medicine Humans Obstetrics business.industry Smoking Infant Newborn Editorials Infant DNA Methylation medicine.disease Ascorbic acid 030104 developmental biology medicine.anatomical_structure Maternal Exposure Prenatal Exposure Delayed Effects Cord blood Dietary Supplements DNA methylation Female business |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 196:745-755 |
| ISSN: | 1535-4970 1073-449X |
| Popis: | 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 demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, 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 1 year of age.To determine whether 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.Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing.The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs.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. |
| Databáze: | OpenAIRE |
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