Pathways of vitamin A delivery to the embryo: insights from a new tunable model of embryonic vitamin A deficiency.
Circulating retinoids (vitamin A and its derivatives) are found predominantly as retinol bound to retinol-binding protein (RBP), which transports retinol from liver stores to target tissues, or as retinyl ester incorporated in lipoproteins of dietary origin. The transport of retinoids from maternal to fetal circulation is poorly understood, especially under conditions of inadequate dietary vitamin A intake. Here we present RBP-/- mice as a tunable model of embryonic vitamin A deficiency. This model has enabled us to analyze metabolic links between maternal nutrition and retinoid delivery to the fetus. Our data show that retinol-RBP is the primary contributor to fetal development, whereas retinyl ester are largely responsible for accumulation of fetal retinoid stores. Furthermore, these studies indicate the importance of embryonic RBP in distributing vitamin A to certain developing tissues under restrictive diets. We also show differences among developing tissues in their dependency on the embryonic retinol-RBP pathway. Finally, we demonstrate that accumulation of embryonic vitamin A stores does not depend on the expression of RBP in the fetal liver.
Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Loredana
L
Quadro
Leora
L
Hamberger
Max E
ME
Gottesman
Fengwei
F
Wang
Vittorio
V
Colantuoni
William S
WS
Blaner
Cathy L
CL
Mendelsohn
D000818:Animals; D001692:Biological Transport; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005260:Female; D005838:Genotype; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D012176:Retinoids / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D014886:Weaning
D012176:Retinoids; D012177:Retinol-Binding Proteins; D014801:Vitamin A