title: High Preformed Vitamin A Intake during Pregnancy Prevents Embryonic Accumulation of Intact β-Carotene from the Maternal Circulation in Mice.
abstract: BACKGROUND
  The vitamin A precursor β-carotene (BC) promotes mammalian embryonic development by serving as a source of retinoids (vitamin A derivatives) to the developing tissues. In the Western world, increased consumption of dietary supplements, including vitamin A and BC, is common; however, the consequences of maternal high preformed vitamin A intake on embryonic uptake and metabolism of BC are poorly understood.
  
  
  OBJECTIVE
  This study investigated vitamin A and BC metabolism in developing mouse tissues after a single BC administration to pregnant wild-type (WT) mice fed purified diets with different vitamin A concentrations.
  
  
  METHODS
  WT dams fed a sufficient vitamin A (VA-S; 4.2 μg of retinol/g of diet), high vitamin A (VA-H; 33 μg of retinol/g of diet), or excess vitamin A (VA-E; 66 μg of retinol/g of diet) diet throughout gestation were intraperitoneally injected with BC or vehicle at 13.5 d postcoitum (dpc). At 14.5 dpc, retinoid and BC concentrations in maternal serum and liver, placenta, and embryo were quantified by HPLC; expressions of genes controlling retinoid and BC homeostasis were analyzed by quantitative polymerase chain reaction. Maternal lipoprotein BC concentrations were analyzed by density gradient ultracentrifugation followed by HPLC.
  
  
  RESULTS
  Intact BC was undetectable only in embryos from VA-E + BC dams. Relative to the VA-S + vehicle group, placentas from VA-S + BC dams showed 39% downregulation of LDL-receptor-related protein 1 (Lrp1 ); 35% downregulation of VLDL receptor (Vldlr); 56% reduced mRNA expression of β-carotene 15,15'-oxygenase (Bco1); and 80% upregulation of β-carotene 9',10'-oxygenase (Bco2). Placental cytochrome P450, family 26, subfamily A, polypeptide 1 (Cyp26A1) was upregulated 2-fold in the VA-E group compared with the VA-S group, regardless of maternal treatment.
  
  
  CONCLUSIONS
  In mice, transfer of intact BC to the embryo is attenuated by high tissue vitamin A concentrations. Maternal vitamin A intake and BC availability activate a placental transcriptional response to protect the embryo from retinoid and carotenoid excess.
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ.
authors.forename: Lesley
authors.initials: L
authors.lastname: Wassef
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ.
authors.forename: Varsha
authors.initials: V
authors.lastname: Shete
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ.
authors.forename: Brianna
authors.initials: B
authors.lastname: Costabile
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Rodas
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ quadro@aesop.rutgers.edu.
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000737:chemistry; D039382:Maternal Nutritional Physiological Phenomena; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019207:beta Carotene / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D012333:RNA, Messenger; D019207:beta Carotene; D014801:Vitamin A
keywords: embryo; maternal-fetal β-carotene metabolism; placenta; retinoids; vitamin A