Experimental intrauterine growth retardation alters renal development

Abstract

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation (IUGR), resulting in small-for-gestational-age, asymmetric newborns. IUGR neonates experience higher morbidity and mortality rates, as well as a possible contribution towards late sequelae, such as hypertension, and cardiovascular disease in adulthood. To simulate vascular placental insufficiency, an experimental rabbit IUGR model was used. Intrauterine growth retardation was achieved by ligation of 25-30% uteroplacental vessels of half of the fetuses during the last third of gestation. Ischemic fetuses were significantly small, asymmetric, and had a disproportionately small body with a relatively large head. The kidneys from all groups were analyzed for relative estimated glomeruli number (REGN) using an unbiased blind design. The glomeruli number was significantly reduced in the asymmetric IUGR rabbit fetuses, probably due to decreased renal vascular supply. Our results support the concept that the reduced number of glomeruli may contribute to impaired renal function, thus predisposing to neonatal renal dysfunction and late sequelae, such as adult hypertension. This study emphasizes the clinical importance of early IUGR diagnosis and prevention.

Nephron Endowment and Filtration Surface Area in the Kidney after Growth Restriction of Fetal Sheep

“…The induction of IUGR by UPE did not result in a reduction in the number of nephrons, which raises some interesting issues as to the influence of the timing of growth restriction. IUGR has been reported as causing a reduction in nephron numbers in rats (2, 3), rabbits (15), pigs (16), sheep (17), and even human infants (1). Surprisingly, in our study this was not the case when IUGR was induced by UPE.…”

Sex differences in the fetal programming of hypertension

“…Different animal models include dietary undernutrition induced by global food restriction (9,10) or protein restriction during gestation (11,12,13,14,15), maternal hypoxia during gestation (16,17), placental insufficiency (18,19,20,21,22), or prenatal glucocorticoid treatment (23,24).…”

“…Nephron number is reduced in models induced by nutrimental insult in the rat (13,14,15), sheep (12), or microswine (47), and in models induced by placental insufficiency in the rat (21) and rabbit (19). Placental insufficiency in the rat leads to marked reductions in nephron number associated with significant increases in renal apoptosis and expression of key apoptosis genes and in the IUGR offspring (48).…”

Neonatal high protein intake enhances neonatal growth without significant adverse renal effects in spontaneous IUGR piglets

“…In IUGR rat offspring, we and others have shown that early neonatal overfeeding or an elective neonatal high protein diet affect renal structure and functions as early as during the neonatal period with significant renal hypertrophy, renal overweight, proteinuria, and glomerular sclerosis (Bassan et al. 2000; Boubred et al. 2009, Luycks et al 2009).…”