Department of Food Science and Rutgers Center for Lipid Research; Rutgers University, New Brunswick, NJ 08901, USA
*Corresponding author:
Loredana Quadro
Department of Food Science and
Rutgers Center for Lipid Research
Rutgers University, New Brunswick
NJ, 08901,
USA Tel: +1 848 932 5491 Fax: +1 732 932 6776 E-mail: quadro@aesop.rutgers.
edu
Received July 27, 2012; Accepted July 30, 2012; Published August 01, 2012
Citation: Kim YK, Quadro L (2012) Who Needs β-Carotene? A focus on Embryonic
Development. J Nutr Food Sci 2:e113. doi:10.4172/2155-9600.1000e113
Vitamin A is an essential nutrient that is required to support many
crucial biological functions, including reproduction and embryonic
development [1]. Mammals acquire retinoids (vitamin A and its
derivatives) from the diet, either as preformed vitamin A (retinol,
retinyl ester and small amount of retinoic acid) from meat and dairy
products, or as provitamin A carotenoids (β-carotene, α-carotene and
β-cryptoxanthin) from fruits and vegetables [1,2]. β-carotene is the
most abundant and well characterized provitamin A carotenoid in
human diet. In the Western countries, it contributes to about 30% of
the vitamin A intake, and for certain populations it represents the most
abundant source of vitamin A [3,4].
According to the World Health Organization, Vitamin A
Deficiency (VAD) is the leading cause of preventable blindness in
children and increases their risk of disease, stunted growth, and death
from severe infections [5,6]. About 250 million pre-school children
are estimated to be vitamin A-deficient worldwide. In addition, almost
20 million pregnant women are estimated to be vitamin A-deficient,
thus severely hindering the growth, development, and health of the
baby [5,6]. Supplementation of infants and children as well as maternal
supplementation before, during, and after pregnancy with vitamin A or
β−carotene has been shown to improve development and infant growth
and to reduce the incidence of premature birth, external birth defects,
and infant infectious morbidity and mortality [4].
Surprisingly, vitamin A deficiency is a problem that afflicts not
only the developing world, but also industrialized countries. Intake of
preformed vitamin A is inadequate in a substantial part of the general
population, with various groups being particularly at risk. These
include people on a poor or highly restrictive dietary regimen like
young individuals, pregnant and lactating women [3,4]. Notably, 3%
of all children born in the United States have a major malformation
at birth, and 70% of these are of unknown etiology [7]. It is a general
consensus that both pre-formed vitamin A and β−carotene are required
to meet the dietary needs of such vitamin [3].
In order to function as vitamin A, β-carotene can be converted into
retinoids (vitamin A and its derivatives) by two possible mechanisms:
1. Symmetric cleavage of β-carotene at the 15, 15’ -carbon double bond
mediated by β,β-carotene-15,15’-oxygenase (CMOI or BCMOI) to give
rise to two molecules of retinaldehyde [8]. 2. Asymmetric cleavage
of β-carotene by β,β-carotene-9’,10’-oxygenase (CMOII or BCDOII)
to generate a β-ionone ring and apocarotenals, which in turn can
produce one molecule of retinaldehyde upon chain shortening [8].
Retinaldehyde can be oxidized into retinoic acid, the biologically active
form of vitamin A and the ligand of specific nuclear receptors (RARs
and RXRs) that regulate the transcription of hundreds of genes, many of
which are crucial to proper embryonic development [9]. Retinaldehyde
can also be reduced to retinol and then esterified by Lecithin:Retinol
Acyltransferase (LRAT) into retinyl ester, the tissue retinoid storage
form [10].
The developing embryo relies on different forms of retinoids
circulating into the maternal bloodstream to fulfill its retinoids needs
for proper embryogenesis [11]. In humans, up to about 40% of the
dietary β-carotene circulates in its intact form in the bloodstream [2,12]. Therefore, the question arises as to whether intact β-carotene
can be used to generate retinoids locally in the developing tissues,
where the cleavage enzymes are expressed [13]. Recent study from our
laboratory has revealed the fundamental mechanisms of β-carotene
action during development. We have unequivocally demonstrated the
ability of the developing embryo to take up, metabolize and utilize
intact β-carotene from the maternal circulation. Loss of CMOI function
studies in an established model of mouse VAD, such as mice lacking
Retinol-Binding Protein (RBP), the sole specific carrier for retinol in
the bloodstream [14-16], revealed that lack of CMOI in the developing
tissues further exacerbates the severity of the embryonic malformations
[13]. This severe embryonic phenotype was accompanied by reduced
levels of retinoids and was due to the lack of CMOI in the developing
tissues [13]. Using this model, we also demonstrated in vivo that intact
β-carotene circulating in the maternal bloodstream crosses the placenta,
and that embryonic CMOI generates retinoids from β-carotene in
the developing tissues [13]. Indeed, CMOI+/-RBP-/- embryos from
double knockout dams deprived of vitamin A throughout gestation
and supplemented with β-carotene, showed a reduced frequency
of developmental defects and increased embryonic retinoid levels,
compared to un-supplemented animals [13].
Our study provides the first in vivo evidence that intact β-carotene
circulating in the maternal bloodstream is an alternative local source
of retinoids for the developing mammalian tissues. Giving that intact
β−carotene is present in the human circulation [2,12] and that it is
generally considered “safer” than preformed vitamin A, as both its
intestinal uptake and cleavage are regulated by retinoic acid to prevent
toxicity [17,18], our data support and provide the molecular basis for
the current recommendation of supplementing pregnant women with
β-carotene, not only in the developing countries but also in the western
world [3].
Grants R01HD057493 and R01HD057493-02S1 from the U.S.
National Institute of Health (NIH) supported our work on β-carotene
metabolism in the developing tissues.
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