46
L. Quadro and E. K. Spiegler
Effects of β-Apocarotenoids on Mammalian Embryogenesis
β-apocarotenoids are not solely generated upon enzymatic cleavage of β-carotene.
They are also formed by spontaneous oxidation of carotenoids in mammalian tissues and foods where they can be relatively abundant (Fleshman et al. 2011; Kopec
et al. 2010; Shmarakov et al. 2010). β-apo-10
carotenoids clearly can be taken up
by the placenta, act within it and be transferred to the fetus (Costabile et al. 2016).
The effects of these oxidized carotenoid metabolites on mammalian embryogenesis
remain to be fully established. However, recently, Spiegler and colleagues demonstrated that maternal β-apo-10
-carotenal supplementation in a mouse model of severe
VA deficiency (Bco2
−/ − Rbp
−/ − mice) restored normal development and resulted in
the birth of phenotypically normal live pups that survived to adulthood and were
fertile (Spiegler et al. 2018). These data clearly indicate that β-apocarotenoids can
sustain embryonic survival and development, at least during severe gestational VA
deficiency (Spiegler et al. 2018).
Relevance
It is now clear that multiple pathways deliver VA to the fetus and that various retinoid
forms are utilized by the developing embryo. Such a redundancy is not a surprise.
Both VA deficiency and excess result in congenital malformations and hence in
reproductive failure. Thus, the transfer of retinoids and pro-VA carotenoids must be
optimized to account for the fluctuations of the maternal VA status and/or the dietary
availability of this essential nutrient. How common are these fluctuations?
VA deficiency is the third-most-common nutritional deficiency in the world,
affecting millions of pregnant women and hundreds of millions of children in developing countries (Stevens et al. 2015). When it does not lead to congenital defects or
early embryonic lethality, maternal VA deficiency increases the risk of complications
pre- and post-partum, such as preterm delivery, maternal infections, night blindness,
anemia and serious immune impairments, making VA-deficient individuals more
susceptible to infectious diseases and death (Sommer and Vyas 2012; Reifen and
Ghebremeskel 2001; Zhang et al. 2014). In industrialized countries, overt VA deficiency is rare, even though emerging data suggest that marginal or subclinical VA
deficiency may be more frequent than expected, especially in areas of low income
and poor socioeconomic status that are associated with malnutrition (Garretto et al.
2019; Hanson et al. 2018; Bird et al. 2017) and surprisingly, among obese people
(Trasino et al. 2015).
Understanding the molecular and physiological mechanisms that modulate the
maternal-fetal metabolism and transfer of this essential nutrient is of utmost relevance
to human health. This knowledge will ultimately help to reduce the incidence of birth
defects associated with abnormal maternal intakes of micronutrients such as vitamins,
L. Quadro and E. K. Spiegler
Effects of β-Apocarotenoids on Mammalian Embryogenesis
β-apocarotenoids are not solely generated upon enzymatic cleavage of β-carotene.
They are also formed by spontaneous oxidation of carotenoids in mammalian tissues and foods where they can be relatively abundant (Fleshman et al. 2011; Kopec
et al. 2010; Shmarakov et al. 2010). β-apo-10
carotenoids clearly can be taken up
by the placenta, act within it and be transferred to the fetus (Costabile et al. 2016).
The effects of these oxidized carotenoid metabolites on mammalian embryogenesis
remain to be fully established. However, recently, Spiegler and colleagues demonstrated that maternal β-apo-10
-carotenal supplementation in a mouse model of severe
VA deficiency (Bco2
−/ − Rbp
−/ − mice) restored normal development and resulted in
the birth of phenotypically normal live pups that survived to adulthood and were
fertile (Spiegler et al. 2018). These data clearly indicate that β-apocarotenoids can
sustain embryonic survival and development, at least during severe gestational VA
deficiency (Spiegler et al. 2018).
Relevance
It is now clear that multiple pathways deliver VA to the fetus and that various retinoid
forms are utilized by the developing embryo. Such a redundancy is not a surprise.
Both VA deficiency and excess result in congenital malformations and hence in
reproductive failure. Thus, the transfer of retinoids and pro-VA carotenoids must be
optimized to account for the fluctuations of the maternal VA status and/or the dietary
availability of this essential nutrient. How common are these fluctuations?
VA deficiency is the third-most-common nutritional deficiency in the world,
affecting millions of pregnant women and hundreds of millions of children in developing countries (Stevens et al. 2015). When it does not lead to congenital defects or
early embryonic lethality, maternal VA deficiency increases the risk of complications
pre- and post-partum, such as preterm delivery, maternal infections, night blindness,
anemia and serious immune impairments, making VA-deficient individuals more
susceptible to infectious diseases and death (Sommer and Vyas 2012; Reifen and
Ghebremeskel 2001; Zhang et al. 2014). In industrialized countries, overt VA deficiency is rare, even though emerging data suggest that marginal or subclinical VA
deficiency may be more frequent than expected, especially in areas of low income
and poor socioeconomic status that are associated with malnutrition (Garretto et al.
2019; Hanson et al. 2018; Bird et al. 2017) and surprisingly, among obese people
(Trasino et al. 2015).
Understanding the molecular and physiological mechanisms that modulate the
maternal-fetal metabolism and transfer of this essential nutrient is of utmost relevance
to human health. This knowledge will ultimately help to reduce the incidence of birth
defects associated with abnormal maternal intakes of micronutrients such as vitamins,