Maternal Malnutrition in Mice Impairs Nephrogenesis by Disrupting DNA Methylation of Regulatory Regions
Maternal caloric restriction during pregnancy significantly impacts kidney development, influencing susceptibility to chronic kidney disease in adulthood. This study explores DNA methylation changes in nephron progenitor cells resulting from caloric restriction and their implications for kidney health. Global DNA hypomethylation is observed in nephron progenitors from caloric-restricted embryos, with specific genomic regions displaying distinct methylation patterns, including hypomethylation and hypermethylation. Differentially methylated regions exhibit enhanced chromatin accessibility, indicating biological relevance. Hypomethylated regions are enriched for genes associated with developmental processes, reflecting changes in gene expression and highlighting their functional relevance in kidney development. The study also reveals that supplementing methionine, an essential amino acid, restores disrupted DNA methylation patterns, particularly in enhancer regions, emphasizing methionine's critical role in regulating nephron progenitor cell epigenetics and ensuring proper kidney development. The intricate relationship between maternal nutrition, dynamic DNA methylation, and kidney development is highlighted, emphasizing the enduring impact of early-life nutritional challenges on kidney function. This research elucidates epigenetic mechanisms as mediators for the lasting effects of maternal caloric restriction on kidney health. The study contributes valuable insights into the origins of chronic kidney diseases during early developmental stages, offering potential interventions to mitigate adverse outcomes. Overall design: Methylation profiling by high throughput DNA sequencing from nephron progenitor cells was acquired from 2 experimental groups each containing 4 samples. Pregnant females were randomly assigned to either a caloric restriction diet (CRD) group or a control, unrestricted diet (URD) group for the duration of the experiment. On embryonic day seventeen (E17.5), the embryonic kidneys were taken, the NPCs were sorted, and the DNA was extracted. Bisulfite conversion of genomic DNA and reduced representation bisulfite sequencing were performed.