TY - JOUR
T1 - Maternal folate depletion and high-fat feeding from weaning affects DNA methylation and DNA repair in brain of adult offspring
AU - Langie, Sabine A S
AU - Achterfeldt, Sebastian
AU - Gorniak, Joanna P.
AU - Halley-Hogg, Kirstin J A
AU - Oxley, David
AU - Van Schooten, Frederik J.
AU - Godschalk, Roger W L
AU - McKay, Jill A.
AU - Mathers, John C.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - The mechanisms through which environmental and dietary factors modulate DNA repair are still unclear but may include dysregulation of gene expression due to altered epigenetic markings. In a mouse model, we investigated the effect of maternal folate depletion during pregnancy and lactation, and high-fat feeding from weaning, on base excision repair (BER) and DNA methylation and expression of selected BER-related genes in the brain of adult offspring. While folate depletion did not affect BER activity of the mothers, BER increased in the offspring at weaning (P=0.052). In the long term, as observed in 6-mo-old offspring, the double insult, i.e., maternal low-folate supply and high-fat feeding from weaning, decreased BER activity significantly in the cortex, cerebellum, hippocampus, and subcortical regions (P<0.017). This fall in BER activity was associated with small changes in methylation or expression of BERrelated genes. Maternal folate depletion led to slightly increased oxidative DNA damage levels in subcortical regions of adult offspring, which may increase sensitivity to oxidative stress and predispose to neurological disorders. In summary, our data suggest that low-folate supply during early life may leave an epigenetic mark that can predispose the offspring to further dietary insults, causing adverse effects during adult life.
AB - The mechanisms through which environmental and dietary factors modulate DNA repair are still unclear but may include dysregulation of gene expression due to altered epigenetic markings. In a mouse model, we investigated the effect of maternal folate depletion during pregnancy and lactation, and high-fat feeding from weaning, on base excision repair (BER) and DNA methylation and expression of selected BER-related genes in the brain of adult offspring. While folate depletion did not affect BER activity of the mothers, BER increased in the offspring at weaning (P=0.052). In the long term, as observed in 6-mo-old offspring, the double insult, i.e., maternal low-folate supply and high-fat feeding from weaning, decreased BER activity significantly in the cortex, cerebellum, hippocampus, and subcortical regions (P<0.017). This fall in BER activity was associated with small changes in methylation or expression of BERrelated genes. Maternal folate depletion led to slightly increased oxidative DNA damage levels in subcortical regions of adult offspring, which may increase sensitivity to oxidative stress and predispose to neurological disorders. In summary, our data suggest that low-folate supply during early life may leave an epigenetic mark that can predispose the offspring to further dietary insults, causing adverse effects during adult life.
KW - Base excision repair
KW - Developmental origin
KW - Epigenetics
U2 - 10.1096/fj.12-224121
DO - 10.1096/fj.12-224121
M3 - Article
C2 - 23603834
AN - SCOPUS:84881168420
VL - 27
SP - 3323
EP - 3334
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 8
ER -