Effect of gestational nutrition on vascular integrity in the murine placenta

Maternal undernutrition is thought to result in smaller offspring and programme disease in later life. It is not known whether gestational nutrition affects development and functioning of placental vessels. The aim of this study was to ascertain if disturbed angiogenesis and junctional integrity were features of the labyrinthine vessels of placenta taken from transgenic Tie2-GFP mice fed either 18% (control) or 9% (low protein; MLP) casein diet. MLP animals showed a significant decrease in fetal weight at E14.5 and in placental and fetal weight at E18.5, however, maternal weight and litter size remained unaffected. Stereological analyses revealed that the fraction of components of the placenta remained similar in both study groups. There was a significant reduction in labyrinthine blood vessel length but not in luminal diameter in the E18.5 MLP group. In both MLP groups, perturbation of vascular endothelial Cadherin and beta-catenin, regulators of junctional integrity, permeability and quiescence, was observed with higher percentage of vessels showing weak or no junctional immunoreactivity. The reduction in length of the labyrinthine vessels and the downregulation of the adhesion molecules suggest that gestational undernutrition causes vascular dysfunction in the murine placenta. This may play a role in the early life programming of disease risk. (C) 2006 Elsevier Ltd. All rights reserved.