48
L. Quadro and E. K. Spiegler
genetically modified animals and well-targeted dietary manipulations should provide
answers to questions about the role of STRA6, the receptor that mediates the placental acquisition of VA from the retinol-RBP complex. The recently reported structure
of STRA6 (Chen et al. 2016) holds promise for unraveling the mechanism of retinol
uptake by the placenta as well as other adult tissues where the receptor is abundantly
expressed. (2) As mentioned earlier, the placental localization of binding proteins
and enzymes involved in retinoid biology has never been systematically analyzed,
although it has been postulated that RBP expressed in the visceral endoderm of the
yolk sac placenta and possibly in the syncytiotrophoblast of the placenta mediates
the embryonic transfer of retinol, either recently ingested (generated through retinyl
ester hydrolysis) (Wassef and Quadro 2011) or mobilized from the liver (and acquired
as such) via maternal circulating RBP (Quadro et al. 1999). A mouse model lacking
RBP specifically at the maternal-fetal barrier would be instrumental in addressing
this question. (3) Whether the placenta also secretes retinyl esters towards the fetal
circulation has never been directly investigated. Of note, the human placenta assembles and secretes apolipoprotein B-100-containing lipoproteins in vivo and in vitro
(Kamper et al. 2015; Madsen et al. 2004). Thus, it is possible that retinyl esters
incorporated in placental lipoproteins could also be secreted into the fetal circulation. From here, it is assumed that the developing tissues and organs of the embryo
acquire the various retinoid forms by metabolic pathways similar to those occurring
in adult mammalian tissues.
Very little is known about the mechanisms of β-carotene transfer from mother to
fetus, largely because the intracellular trafficking of β-carotene and its compounds is
poorly understood. Currently, the literature suggests that the developing tissues and
organs of the embryo acquire carotenoids by metabolic pathways similar to those
occurring in adult mammalian tissues and linked to the metabolism of lipids.
One potentially important consideration comes to mind when one thinks about
the link between maternal-fetal carotenoid and lipid metabolism. It is intriguing
to speculate that, by modulating placental lipoprotein secretion, β-apocarotenoids
may also ultimately regulate the transfer of other important nutrients carried within
these lipoproteins—for example, fatty acids. Fetal growth is largely dictated by the
availability of nutrients in the maternal circulation transported to the fetus across the
placenta, and birth weight (as a consequence of fetal growth) has been correlated
with the risk of developing diseases later in life (Geraghty et al. 2016). In addition to
the well-known role of glucose, the role of fatty acids is also emerging as essential
for intrauterine growth (Herrera and Ortega-Senovilla 2014). Fetal fatty acids are
either synthesized de novo or taken up from the maternal circulation, where they
are found either in free form, bound to albumin, or as triglycerides in lipoproteins.
Most dietary lipids enter the circulation through chylomicrons and, along with hepatic
VLDL particles, account for total circulating triglycerides. The lipase-generated free
fatty acids from chylomicrons and VLDL particles can be taken up by the placenta,
which in turn re-secretes them into the fetal bloodstream via placenta-synthesized
lipoproteins (Chirala et al. 2003). Interestingly, maternal diet-derived triglycerides
can be transported to the fetus in amounts correlating with the maternal lipid intake
(Rebholz et al. 2011). Moreover, high maternal serum triglyceride concentrations
L. Quadro and E. K. Spiegler
genetically modified animals and well-targeted dietary manipulations should provide
answers to questions about the role of STRA6, the receptor that mediates the placental acquisition of VA from the retinol-RBP complex. The recently reported structure
of STRA6 (Chen et al. 2016) holds promise for unraveling the mechanism of retinol
uptake by the placenta as well as other adult tissues where the receptor is abundantly
expressed. (2) As mentioned earlier, the placental localization of binding proteins
and enzymes involved in retinoid biology has never been systematically analyzed,
although it has been postulated that RBP expressed in the visceral endoderm of the
yolk sac placenta and possibly in the syncytiotrophoblast of the placenta mediates
the embryonic transfer of retinol, either recently ingested (generated through retinyl
ester hydrolysis) (Wassef and Quadro 2011) or mobilized from the liver (and acquired
as such) via maternal circulating RBP (Quadro et al. 1999). A mouse model lacking
RBP specifically at the maternal-fetal barrier would be instrumental in addressing
this question. (3) Whether the placenta also secretes retinyl esters towards the fetal
circulation has never been directly investigated. Of note, the human placenta assembles and secretes apolipoprotein B-100-containing lipoproteins in vivo and in vitro
(Kamper et al. 2015; Madsen et al. 2004). Thus, it is possible that retinyl esters
incorporated in placental lipoproteins could also be secreted into the fetal circulation. From here, it is assumed that the developing tissues and organs of the embryo
acquire the various retinoid forms by metabolic pathways similar to those occurring
in adult mammalian tissues.
Very little is known about the mechanisms of β-carotene transfer from mother to
fetus, largely because the intracellular trafficking of β-carotene and its compounds is
poorly understood. Currently, the literature suggests that the developing tissues and
organs of the embryo acquire carotenoids by metabolic pathways similar to those
occurring in adult mammalian tissues and linked to the metabolism of lipids.
One potentially important consideration comes to mind when one thinks about
the link between maternal-fetal carotenoid and lipid metabolism. It is intriguing
to speculate that, by modulating placental lipoprotein secretion, β-apocarotenoids
may also ultimately regulate the transfer of other important nutrients carried within
these lipoproteins—for example, fatty acids. Fetal growth is largely dictated by the
availability of nutrients in the maternal circulation transported to the fetus across the
placenta, and birth weight (as a consequence of fetal growth) has been correlated
with the risk of developing diseases later in life (Geraghty et al. 2016). In addition to
the well-known role of glucose, the role of fatty acids is also emerging as essential
for intrauterine growth (Herrera and Ortega-Senovilla 2014). Fetal fatty acids are
either synthesized de novo or taken up from the maternal circulation, where they
are found either in free form, bound to albumin, or as triglycerides in lipoproteins.
Most dietary lipids enter the circulation through chylomicrons and, along with hepatic
VLDL particles, account for total circulating triglycerides. The lipase-generated free
fatty acids from chylomicrons and VLDL particles can be taken up by the placenta,
which in turn re-secretes them into the fetal bloodstream via placenta-synthesized
lipoproteins (Chirala et al. 2003). Interestingly, maternal diet-derived triglycerides
can be transported to the fetus in amounts correlating with the maternal lipid intake
(Rebholz et al. 2011). Moreover, high maternal serum triglyceride concentrations