母体低栄養(NR)後腎ではDNAメチル化を担うDNA基転移酵素のうちDNMT1が減少しており, 全般的DNAメチル化低下の一因と考えられた。また器官培養系でDNAメチル化を抑制すると尿管芽分岐, 腎成長が抑制され, 葉酸をNRラットに補給すると胎仔の尿管芽分岐, 腎サイズ減少, 糸球体密度, DNAメチル化低下が改善された。さらに器官培養系で葉酸を含むメチル基ドナー欠乏は尿管芽分岐, 腎成長を抑制し, NR後腎を葉酸存在下で培養すると病態が改善された。以上からDNAメチル化は腎発生に必要であり, NR後腎の病態の一因はDNAメチル化低下であると考えられた。また葉酸によるネフロン数減少の予防の可能性が示された。
In metanephroi from embryos of nutrient restricted rat dams, global DNA methylation is reduced, and the reduction in DNA methyltransferase 1, an enzyme that maintains DNA cytosine methylation, was thought to be the cause. DNA methylation inhibitor 5-Aza-2'-deoxycytidine inhibited ureteric branching and metanephros growth in organ culture. On the other hand, folic acid supplementation to nutrient restricted mothers improved the reduction in ureteric branching, kidney size, glomerular density, and DNA methylation in the fetal kidney. Medium deficient in methyl donors including folic acid decreased ureteric branching and metanephros growth in organ culture, whereas the addition of folic acid to the medium improved the phenotype of metanephroi of fetuses from nutrient restricted mothers. Thus DNA methylation is necessary for kidney development and maternal folic acid supplementation may prevent low nephron number due to maternal nutrient restriction.
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