β-apo-10'-carotenoids support normal embryonic development during vitamin A deficiency.

Scientific reports (2018-06-13)
Elizabeth Spiegler, Youn-Kyung Kim, Beatrice Hoyos, Sureshbabu Narayanasamy, Hongfeng Jiang, Nicole Savio, Robert W Curley, Earl H Harrison, Ulrich Hammerling, Loredana Quadro

Vitamin A deficiency is still a public health concern affecting millions of pregnant women and children. Retinoic acid, the active form of vitamin A, is critical for proper mammalian embryonic development. Embryos can generate retinoic acid from maternal circulating β-carotene upon oxidation of retinaldehyde produced via the symmetric cleavage enzyme β-carotene 15,15'-oxygenase (BCO1). Another cleavage enzyme, β-carotene 9',10'-oxygenase (BCO2), asymmetrically cleaves β-carotene in adult tissues to prevent its mitochondrial toxicity, generating β-apo-10'-carotenal, which can be converted to retinoids (vitamin A and its metabolites) by BCO1. However, the role of BCO2 during mammalian embryogenesis is unknown. We found that mice lacking BCO2 on a vitamin A deficiency-susceptible genetic background (Rbp4-/-) generated severely malformed vitamin A-deficient embryos. Maternal β-carotene supplementation impaired fertility and did not restore normal embryonic development in the Bco2-/-Rbp4-/- mice, despite the expression of BCO1. These data demonstrate that BCO2 prevents β-carotene toxicity during embryogenesis under severe vitamin A deficiency. In contrast, β-apo-10'-carotenal dose-dependently restored normal embryonic development in Bco2-/-Rbp4-/- but not Bco1-/-Bco2-/-Rbp4-/- mice, suggesting that β-apo-10'-carotenal facilitates embryogenesis as a substrate for BCO1-catalyzed retinoid formation. These findings provide a proof of principle for the important role of BCO2 in embryonic development and invite consideration of β-apo-10'-carotenal as a nutritional supplement to sustain normal embryonic development in vitamin A-deprived pregnant women.

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Ethylenediaminetetraacetic acid disodium salt dihydrate, suitable for electrophoresis, for molecular biology, 99.0-101.0% (titration)
Kolliphor® EL, pH range 6.0-8.0