Nephron endowment is reduced by prenatal placental restriction but can be restored by a normal lactational environment
Background: Adverse prenatal and early postnatal environments are known to increase the risk of developing adult hypertension. This study evaluated the impact of placental restriction in utero on adult nephron endowment and renal angiotensin II type 1 receptor (AT1R) gene expression. In addition, we examined lactational influences, by performing cross-fostering studies.
Methods: Bilateral uterine vessel ligation (Restriction-R) or sham surgery (Control-C) was performed on day 18 of gestation in Wistar Kyoto rats. Control, Reduced (RED- litter size of Control to 5, to match R) and Restricted pups were cross-fostered onto a C or R mother on postnatal day 1. Blood pressure, nephron number and relative renal AT1R mRNA expression were measured at 5-6 months in male offspring.
Results: R-on-R offspring had reduced birth weight and hypertension (+15mmHg,), which correlated with a nephron deficit (-26%) and glomerular hypertrophy. Providing normal lactation to Restricted offspring increased body weight during lactation and corrected the nephron deficit and hypertension in adults. Interestingly, Red-on-R pups with a normal prenatal, but Restricted lactational, environment developed hypertension (+15mmHg) with increased renal AT1aR and AT1bR mRNA expression (+58-66%), but not low nephron number.
Conclusions: Poor prenatal and postnatal environments programmed hypertension in males via a nephron deficit. This hypertension was corrected by a normal lactational environment after placental restriction via restoration of nephron number, highlighting the importance of postnatal nutrition in the regulation of blood pressure. This study provides novel insights into the contributions of the prenatal and postnatal environments to the renal mechanisms underlying programmed hypertension.