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Uteroplacental insufficiency in rats induces renal apoptosis and delays nephrogenesis completion

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Acta Physiologica

Published online on


Aim Uteroplacental insufficiency in rats reduces nephron endowment, leptin concentrations and programs cardiorenal disease in offspring. Cross‐fostering growth restricted (Restricted) offspring onto a mother with normal lactation restores leptin concentrations and nephron endowment. This study aimed to determine if the reduced nephron endowment in Restricted offspring is due to delayed glomerular formation and dysregulation of renal genes regulating branching morphogenesis, apoptosis or leptin signalling. Furthermore, we aimed to investigate if cross‐fostering Restricted offspring onto Control mothers could improve glomerular maturation and restore renal gene abundance. Methods Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery on gestation day 18 (E18). Kidneys were collected at E20, postnatal day 1 (PN1) and PN7. An additional cohort was cross‐fostered onto separate mothers at birth and kidneys collected at PN7. Results Kidneys were lighter in the Restricted group, but weight was restored with cross‐fostering. At E20, Bax, Flt1 and Vegfa abundance were increased in Restricted offspring, while Ret and Bcl2 transcripts were increased only in Restricted females. At PN7, Gdnf and Ret abundance were higher in Restricted offspring, as was Casp3. Restricted offspring had a wider nephrogenic zone with more immature glomeruli suggesting a delayed or extended nephrogenic period. Cross‐fostering had subtle effects on gene abundance and glomerular maturity. Conclusion Uteroplacental insufficiency induced apoptosis in the developing kidney and delayed and extended nephrogenesis. Cross‐fostering Restricted offspring onto Control mothers had beneficial effects on kidney growth and renal maturity, which may contribute to the restoration of nephron endowment. This article is protected by copyright. All rights reserved.