Fetal growth restriction leads to prolonged nephrogenesis and gene dysregulation in the adult kidney.

چکیده اصلی

Low birthweight increases chronic kidney disease (CKD) risk. Using a gestational low protein (LP) mouse model, we hypothesized that protein restriction would alter nephrogenesis and adult gene expression. Pregnant CD-1 dams received normal protein (NP) or LP diets. Pups were studied on postnatal days 2-7 to assess the nephron progenitor cell population. Adult mice underwent transdermal GFR measurement and histologic evaluation, bulk RNA sequencing, and cationic-ferritin-enhanced MRI. Nephrogenesis was protracted in LP mice compared with NP mice. Adult LP mice had fewer glomeruli. LP males had lower GFR and more atubular glomeruli without glomerular hypertrophy. LP males demonstrated down-regulated Gfrα1 and Aldh1a1 LP females demonstrated Gata3 down-regulation. LP offspring exhibited prolonged postnatal nephrogenesis with a lower glomerular number as adults, indicating an extended developmental window did not compensate for their reduced nephron endowment at birth. Suppression of the retinoic acid-GDNF signaling pathway was present in LP males. These findings identify a potential early life therapeutic window to mitigate CKD risk in growth-restricted offspring.

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