High Preformed Vitamin A Intake during Pregnancy Prevents Embryonic Accumulation of Intact β-Carotene from the Maternal Circulation in Mice1–3

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...

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Veröffentlicht in:The Journal of nutrition 2015-07, Vol.145 (7), p.1408-1414
Hauptverfasser: Wassef, Lesley, Shete, Varsha, Costabile, Brianna, Rodas, Rebeka, Quadro, Loredana
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-3166
1541-6100
DOI:10.3945/jn.114.207043