Abstract: SA-PO0676
Fetal Growth Restriction Alters Nephrogenesis and Transcriptome of Kidneys in Adults
Session Information
- Pediatric Nephrology: Transplantation, Hypertension, AKI, Genetics, and Developmental Diseases
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Timberline, Sage, University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Indugula, Shalini, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Schuh, Meredith Posner, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Yarlagadda, Sunitha, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Deronde, Kimberly, University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Bennett, Kevin M., Washington University in St Louis, St. Louis, Missouri, United States
- Suzuki, Masako, Texas A&M University System, College Station, Texas, United States
- Sista Kameshwar, Ayyappa Kumar, Texas A&M University System, College Station, Texas, United States
- Reidy, Kimberly J., Montefiore Einstein Medical Center, New York, New York, United States
- Charlton, Jennifer R., University of Virginia School of Medicine, Charlottesville, Virginia, United States
Background
Low birthweight (LBW) is a risk factor for chronic kidney disease (CKD). LBW has been modeled in mice exposed to maternal low protein (LP) during gestation, showing risk for CKD is due partly to low nephron number, though mechanisms are unclear. Using this model, we tested the hypotheses that 1) nephrogenesis would be shorter in LP offspring, and 2) that adult kidneys of these mice would exhibit characteristic differential gene expression. These results may identify windows for both injury and therapeutic interventions.
Methods
Pregnant CD-1 dams received a normal protein (NP, 18%) or LP (8%) diet through lactation (Fig 1A). A subset were euthanized on postnatal days (PN) 2–7 (n=2-7/day). Kidneys were stained with PAS. Immunofluorescence assessed SIX2 (progenitor cells), JAG1 (nascent nephron patterning), and LEF1 (Wnt signaling). At 6 weeks, CF-enhanced MRI was used to quantify glomerular number. Bulk RNA sequencing was performed.
Results
LP mice had delayed nephrogenesis: cap mesenchyme and molecular markers persisted until PN5–6, but were absent in NP by PN3–5 (Fig 1B). Regression showed significant differences in slopes (SIX2, p=0.01, Fig 1C; LEF1, p=0.04) and intercepts (JAG1, p<0.0001). Adult LP mice had lower kidney/body weight (Fig 1D) and fewer glomeruli (Fig 1E). We identified 5 upregulated genes, including Col5a1 (fibrosis) and 8 downregulated genes, including Aldh1a1 (oxidative stress) and Gfra1 (hypoplasia), in males (Fig 1F and G). In contrast, most differentially expressed genes (11 genes) were downregulated but two were upregulated (Dgkd, Elf4b) in females.
Conclusion
LP offspring had prolonged nephrogenesis and delayed differentiation, but fewer nephrons. In adulthood, changes such as increased Col5a1 and reduced Aldh1a1 and Gfra1 may contribute to CKD risk. These findings highlight how LP exposure alters kidney development and suggest potential targets for early intervention in growth-restricted individuals.
Funding
- Other NIH Support