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- W2077403402 abstract "Mice developing in an adverse uterine environment lacking endothelial nitric oxide synthase (NOS3) have altered vascular phenotype and are hypertensive later in life. This was reversed by prenatal supplementation with methyl-donor rich diet. Antioxidant enzymes, like superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT), were also upregulated in the kidneys of these offspring. Our aim was to determine whether the altered gene expression of these enzymes might play a role in the altered vascular programming, and whether these changes can be reversed by methyl-donor enriched diet, using a model of vascular programming. Homozygous NOS3 knockout and wild type mice were cross-bred to produce heterozygous offspring developing in a WT mother with a normal uterine environment (KOP) versus offspring from a KO mother lacking a functional NOS3 (KOM). Mothers were placed on a methyl-donor enriched (MD) or control diet (CD) during pregnancy and pups weaning. Offspring were then kept on CD until sacrifice (14 weeks). Offspring kidneys were isolated and RNA extracted for SOD, GPx and CAT gene expression. One-way-ANOVA and Student t-test were used as appropriate for statistical analysis (significance: p<0.05). In male offspring, CAT, GPx and SOD gene expression was significantly lower in the KOM compared with KOP, whether from the CD or MD groups. CAT, GPx expression was lower in female KOM compared with KOP on CD. Female KOM offspring on MD show a significant increased in CAT, GPx and SOD expression compared with KOM on CD to a level similar to KOP on CD (Figure 1A, 1B). An adverse uterine environment lead to altered gene expression of antioxidant genes in the offspring kidney in a gender specific manner, and this effect can be reversed by maternal methyl-donor supplementation. Epigenetic regulation of oxidative stress genes may be responsible for the fetal origin of adult hypertension, opening a window to a new therapeutic approach using folate supplementation." @default.
- W2077403402 created "2016-06-24" @default.
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- W2077403402 date "2013-01-01" @default.
- W2077403402 modified "2023-09-23" @default.
- W2077403402 title "201: The role of candidate oxidative stress genes in the developmental programming of adult disease" @default.
- W2077403402 doi "https://doi.org/10.1016/j.ajog.2012.10.366" @default.
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