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Abstract: PO2289

Preterm Birth in Mice Results in Differential Gene Expression and Premature Cessation of Nephrogenesis

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Cwiek, Aleksandra, University of Virginia, Department of Pediatrics, Division of Nephrology, Charlottesville, Virginia, United States
  • Deronde, Kimberly, University of Virginia, Department of Pediatrics, Division of Nephrology, Charlottesville, Virginia, United States
  • Suzuki, Masako, Albert Einstein College of Medicine, Department of Genetics, New York, New York, United States
  • Reidy, Kimberly J., Children's Hospital at Montefiore, Department of Pediatrics, Division of Nephrology, New York, New York, United States
  • Charlton, Jennifer R., University of Virginia, Department of Pediatrics, Division of Nephrology, Charlottesville, Virginia, United States
Background

Neonates born preterm are at risk of developing chronic kidney disease (CKD). In humans, nephron development is completed by 36 weeks’ gestation and the successful formation of nephrons is dependent on self-renewing niches of cells which reside directly under the kidney capsule in the nephrogenic zone (NZ). Little is known about the fate of these progenitor cells or the other compartments of the kidney following premature birth. The objective of this study was to characterize the effect of premature birth on kidney development in murine model of prematurity. We hypothesize that preterm mice will have a shorter period of postnatal nephrogenesis and gene expression profiles will reflect premature differentiation.

Methods

Timed pregnant CD-1 dams were stratified into 2 cohorts. The preterm group was comprised of 59 pups born by Cesarean section at 18 days post-conception (dpc) and the term group contained 79 pups delivered vaginally at 20 dpc. The mice were euthanized on 20-27 dpc. The presence of the nephrogenic zone was determined on histological sections. Genome-wide expression profiles of 20 dpc mice kidneys were evaluated with RNA-seq in both preterm and term groups (n=3 per group).

Results

At 25-27 dpc, kidney to body weight ratios were significantly lower in preterm cohort. In the kidney, the cap mesenchyme was not detectable in the preterm mice a full day (23 dpc) prior to its cessation in the term mice (24 dpc). The expression profiles of 20 dpc kidneys in the preterm group showed distinct alterations compared to the term group. The differentially expressed genes were enriched in a fat-soluble vitamin (including vitamin A and D) metabolic process related pathways.

Conclusion

In a mouse model of prematurity, there is an early differential expression of genes that may be important in nephrogenesis. The shortened window of nephrogenesis may result in a lower nephron number and future risk for CKD in neonates born preterm.