2 Maternal-Fetal Transfer of Vitamin A …
45
proteasomal degradation do not occur. Within cells, MTP also facilitates the assembly of apoB-containing lipoproteins (chylomicrons and VLDL particles) (Hussain
2014; Fisher 2012). Ultimately, the upregulation of MTP at the mRNA and activity
levels promotes the synthesis of lipoproteins containing β-carotene and their secretion toward the embryo (Costabile et al. 2016; Fig. 2.5). These findings indicate
that the placenta is equipped with a highly regulated molecular machinery (regulated by dietary cues) that, under a normal maternal VA status, favors the transfer of
intact β-carotene (RA precursor) over that of RA. This interpretation is in agreement
with the notion that RA is preferentially synthesized in the developing embryo from
retinoid precursors rather than transferred as such to the embryo (Costabile et al.
2016). However, it contrasts the hypothesis that, in placenta, β-carotene is predominantly used as a precursor of retinol, which is then transferred as such to the embryo
(Dimenstein et al. 1996). Perhaps, under a sufficient maternal VA status, this feedforward mechanism of placental lipoprotein biosynthesis by β-carotene confers an
advantage in transferring β-carotene over other retinoid forms. Indeed, β-carotene
may be considered a “safer” source of retinoids for the developing embryo, given
that, unlike retinol, its uptake and cleavage are highly regulated processes (Lobo
et al. 2013), and therefore is less likely to have toxic effects.
Fig. 2.5 Placental lipoprotein regulation by β-apo-10 carotenoids. Upon β-carotene availability,
placental β,β-carotene 9 ,10 -oxygenase (BCO2) cleaves the pro-VA carotenoid asymmetrically to
generate β-apo-10 carotenoid(s). This metabolite(s) then increase(s) the transcription and activity
of microsomal triglyceride transfer protein (MTP), which in turn stimulates the biosynthesis and
transfer of β-carotene-containing lipoproteins toward the fetal circulation. B100, apolipoprotein
B100; CE, cholesteryl ester; ER, endoplasmic reticulum; TG, triglycerides
45
proteasomal degradation do not occur. Within cells, MTP also facilitates the assembly of apoB-containing lipoproteins (chylomicrons and VLDL particles) (Hussain
2014; Fisher 2012). Ultimately, the upregulation of MTP at the mRNA and activity
levels promotes the synthesis of lipoproteins containing β-carotene and their secretion toward the embryo (Costabile et al. 2016; Fig. 2.5). These findings indicate
that the placenta is equipped with a highly regulated molecular machinery (regulated by dietary cues) that, under a normal maternal VA status, favors the transfer of
intact β-carotene (RA precursor) over that of RA. This interpretation is in agreement
with the notion that RA is preferentially synthesized in the developing embryo from
retinoid precursors rather than transferred as such to the embryo (Costabile et al.
2016). However, it contrasts the hypothesis that, in placenta, β-carotene is predominantly used as a precursor of retinol, which is then transferred as such to the embryo
(Dimenstein et al. 1996). Perhaps, under a sufficient maternal VA status, this feedforward mechanism of placental lipoprotein biosynthesis by β-carotene confers an
advantage in transferring β-carotene over other retinoid forms. Indeed, β-carotene
may be considered a “safer” source of retinoids for the developing embryo, given
that, unlike retinol, its uptake and cleavage are highly regulated processes (Lobo
et al. 2013), and therefore is less likely to have toxic effects.
Fig. 2.5 Placental lipoprotein regulation by β-apo-10 carotenoids. Upon β-carotene availability,
placental β,β-carotene 9 ,10 -oxygenase (BCO2) cleaves the pro-VA carotenoid asymmetrically to
generate β-apo-10 carotenoid(s). This metabolite(s) then increase(s) the transcription and activity
of microsomal triglyceride transfer protein (MTP), which in turn stimulates the biosynthesis and
transfer of β-carotene-containing lipoproteins toward the fetal circulation. B100, apolipoprotein
B100; CE, cholesteryl ester; ER, endoplasmic reticulum; TG, triglycerides