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- W2137227757 abstract "Uteroplacental insufficiency causes intrauterine growth retardation (IUGR), which is associated with adult onset diseases such as hypertension. Previous studies demonstrate that growth retardation in humans and rats decreases glomeruli number; however, the molecular mechanisms responsible for this reduction are unknown. Apoptosis plays a key role in renal organogenesis. We therefore hypothesized that the in utero deprivation associated with uteroplacental insufficiency decreases glomeruli, increases apoptosis, and alters the mRNA levels of key apoptosis-related proteins in full-term IUGR kidneys. To prove this hypothesis, we induced asymmetric IUGR through bilateral uterine artery ligation of the pregnant rat. We found that uteroplacental insufficiency significantly reduced glomeruli number while increasing TUNEL staining and caspase-3 activity in the IUGR kidney. A significant decrease in Bcl-2 mRNA and a significant increase in Bax and p53 mRNA further characterized the IUGR kidney. Because altered p53 CpG methylation affects p53 expression, we analyzed p53 promoter CpG methylation using methylation-sensitive restriction enzymes and real-time PCR. Uteroplacental insufficiency specifically decreased CpG methylation of the renal p53 BstU I site promoter without affecting the Hha I or the Aci I sites. Uteroplacental insufficiency also induced a relative hypomethylation from exon 5 to exon 8, which was associated with deceased mRNA levels of DNMT1. We conclude that uteroplacental insufficiency alters p53 DNA CpG methylation, affects mRNA levels of key apoptosis-related proteins, increases renal apoptosis, and reduces glomeruli number in the IUGR kidney. We speculate that these changes represent mechanisms that contribute to the fetal origins of adult disease." @default.
- W2137227757 created "2016-06-24" @default.
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- W2137227757 date "2003-11-01" @default.
- W2137227757 modified "2023-10-15" @default.
- W2137227757 title "Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney" @default.
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- W2137227757 doi "https://doi.org/10.1152/ajpregu.00201.2003" @default.
- W2137227757 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12869365" @default.
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