Abstract 4370627: Impacts of Parental Protein Malnutrition on Cardiac and Renal Development

Background: Poor maternal nutrition during pregnancy raises the risk of various adult-onset diseases in offspring, including cardiovascular, kidney dysfunction, and hypertension. Here, we examined the morphometric effects of a low-protein diet (LPD) from preconception through birth on the development of the kidney and heart, two crucial organs involved in blood pressure regulation. Hypothesis: Parental LPD leads to oligonephropathy and impaired heart development at birth, increasing the risk for cardiorenal syndrome in adulthood. Methods: CD1 mice were fed a normal-protein diet (NPD; 20% protein) or an LPD (6% protein) for two weeks before mating and throughout gestation. Kidneys and hearts were collected from pups at postnatal day 0 (P0). Morphometric analysis and immunostaining were performed to assess the impact on organ development and glomerular density. Results: Offspring of LPD-fed parents were stunted with a reduced body weight at P0 compared to NPD controls (LPD = 1.02 ± 0.03 g, n = 8 vs. NPD = 1.43 ± 0.04 g; n = 10, p < 0.0001). Kidney weight was lower in the LPD group (LPD = 0.0074 ± 0.0005 g vs NPD = 0.0136 ± 0.0003 g; p < 0.0001). The kidney/body weight ratio was also reduced (LPD = 0.0071 ± 0.0003 vs. NPD = 0.0095 ± 0.0003; p < 0.0002). Average glomerular counts across two 5 µm non-consecutive sections were significantly diminished in LPD offspring at P0 (LPD = 44.9 ± 1.8 vs NPD 59.5 ± 2.5; p < 0.0001), reflecting impaired nephrogenesis. Average heart weight was reduced in the LPD group, but did not reach statistical significance (LPD = 0.0065 ± 0.0003 g vs NPD = 0.0076 ± 0.0004 g; p = 0.081). The heart/body weight ratio was significantly higher in LPD pups (0.0064 ± 0.0003) versus NPD (0.0052 ± 0.0002; p < 0.0052), reflecting differences in proportional cardiac growth due to lower body weight in LPD animals. Conclusion: Parental LPD causes significant reductions in offspring body weight, kidney weight, and nephron endowment at birth, as evidenced by lower glomerular counts. Although heart weight showed a trend toward reduction, the increased heart weight-to-body weight ratio in LPD pups suggests altered cardiac growth proportional to their reduced body size. These developmental changes likely increase susceptibility to hypertension and cardiorenal syndrome in adulthood. Understanding these early-life alterations underscores the importance of nutritional interventions during pregnancy in preventing long-term cardiovascular and renal disease.