Altered Nephron Progenitor Cell Dynamics Drive Long-Term Kidney Abnormalities Following Preterm Birth in Mice
In a mifepristone-induced mouse model, we examined how preterm birth affects nephron endowment and renal injury at P30 and P180. Preterm mice had up to 17% fewer nephrons (p<0.01) and ~25% lower kidney-to-body-weight ratios at both ages (p<0.05), despite ~40% higher body weight by P180. Injury markers were elevated (creatinine ~50% higher, NGAL ~35% higher, urinary albumin approximately doubled, p<0.001, and KIM-1 increased). Glomerular density fell by ~30% at P180, glomeruli were disproportionately medullary, and Bowman's space/capsule ratios suggested filtration defects. Bulk RNA-seq around birth revealed acute activation of cellular stress pathways and transient impairment of nephron progenitor differentiation that resolved within 24 hours, alongside a short-lived rise in progenitor proliferation and an approximately 24-hour extension of nephrogenesis, consistent with a compensatory response. Overall, preterm birth disrupts NPC timing and stress responses, reducing nephron endowment and predisposing to lasting kidney injury, while highlighting a brief postnatal window that may be leveraged to support renal development.