title: Embryonic phenotype, β-carotene and retinoid metabolism upon maternal supplementation of β-carotene in a mouse model of severe vitamin A deficiency.
abstract: We investigated the effect of β-carotene (bC) supplementation during pregnancy in a mouse model of severe vitamin A deficiency, i.e. Lrat-/-Rbp-/- dams maintained on a vitamin A-deficient diet during gestation. bC, a provitamin A carotenoid, can be enzymatically cleaved to form vitamin A for use by the developing embryo. We found that an acute supplementation (13.5 days post coitum, dpc) of bC to Lrat-/-Rbp-/- dams on a vitamin A-deficient diet activated transcriptional mechanisms in the developing tissues to maximize the utilization of bC provided to the dams. Nevertheless, these regulatory mechanisms are inefficient under this regimen, as the embryonic phenotype was not improved. We further investigated the effect of a repeated supplementation of bC during a crucial developmental period (6.5-9.5 dpc) on the above-mentioned mouse model. This treatment improved the embryonic abnormalities, as 40% of the embryos showed a normal phenotype. In addition, analysis of retinoic acid-responsive genes, such as Cyp26a1 in these embryos suggests that bC cleavage results in the production of retinoic acid which then can be used by the embryo. Taken together, these in vivo studies show that bC can be used as a source of vitamin A for severely vitamin A-deficient mammalian embryos.
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, NJ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wassef
authors.forename: E
authors.initials: E
authors.lastname: Spiegler
authors.forename: L
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008431:Maternal-Fetal Exchange / Q000235:genetics; D051379:Mice; D010641:Phenotype; D011247:Pregnancy; D000072516:Retinoic Acid 4-Hydroxylase; D012176:Retinoids / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D014212:Tretinoin / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000235:genetics / Q000378:metabolism*; D019207:beta Carotene / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*
chemical_list: D012176:Retinoids; D019207:beta Carotene; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase
keywords: Embryo; Lrat−/−Rbp−/−; Placenta; Retinoids; Vitamin A deficiency; β-Carotene