2 Maternal-Fetal Transfer of Vitamin A …
41
(1) Recently consumed retinoids within chylomicrons or chylomicron remnants
generated by systemic LPL can be taken up through the catalytic activity of
LPL expressed in the placenta. The hydrolysis of retinyl esters to retinol by
LPL appears to be particularly important for retinoid transfer to the embryo.
Whether LPL is the sole placental enzyme capable of hydrolyzing retinyl esters
remains to be established. It certainly seems to be the predominant one.
(2) The bridging function of placental LPL can also facilitate the uptake of chylomicrons or their remnants; however, further processing of these particles to
make retinoids available for the embryo seems to be rather inefficient.
(3) In the placenta, LPL functions in association with LRP1 and LDLR.
(4) Upon uptake by the maternal liver, recently consumed VA can also be rapidly
re-secreted as retinol-RBP to be delivered to the placenta.
Maternal-Fetal Transfer of VA: Is There a Role for STRA6?
To validate the idea that retinol uptake is mediated by STRA6 (Kawaguchi et al. 2007;
Chen et al. 2016), several laboratories generated STRA6
−/− mice independently
using conventional gene knockout approaches (Terra et al. 2013; Amengual et al.
2014; Ruiz et al. 2012; Zemany et al. 2014). Surprisingly, STRA6
−/− mice are viable
and fertile when maintained on a regular chow diet and are born at a Mendelian
frequency (Terra et al. 2013; Amengual et al. 2014; Ruiz et al. 2012). However,
they display ocular malformations that are characteristic of VA-deficient animals.
Moreover, in young adult mutant mice maintained on a VA-deficient diet, the retinoid
content in the eye is dramatically reduced, and visual function is impaired (Terra
et al. 2013; Amengual et al. 2014; Ruiz et al. 2012). These data are consistent with
a mandatory role of the retinol-RBP-STRA6 pathway for retinoid delivery to the
eye, already evidenced by earlier studies in RBP
−/− mice (Quadro et al. 1999). The
embryonic development and, more generally, fertility of STRA6
−/− mice on a VAdeficient diet during pregnancy have never been investigated. Thus, to date, there
is no unequivocal proof of a role for STRA6 in the retinol-RBP transfer across
the placenta. We predict that, if STRA6 is critical for the retinol-RBP uptake at the
placental barrier, in the absence of dietary VA and of a functional retinol-RBP-STRA6
pathway, embryonic development should be severely hindered.
Maternal-Fetal Transfer of β-Carotene
β-carotene is the most abundant dietary VA precursor, constituting at least 30%
of the VA intake in industrialized countries and often serving as the sole source
41
(1) Recently consumed retinoids within chylomicrons or chylomicron remnants
generated by systemic LPL can be taken up through the catalytic activity of
LPL expressed in the placenta. The hydrolysis of retinyl esters to retinol by
LPL appears to be particularly important for retinoid transfer to the embryo.
Whether LPL is the sole placental enzyme capable of hydrolyzing retinyl esters
remains to be established. It certainly seems to be the predominant one.
(2) The bridging function of placental LPL can also facilitate the uptake of chylomicrons or their remnants; however, further processing of these particles to
make retinoids available for the embryo seems to be rather inefficient.
(3) In the placenta, LPL functions in association with LRP1 and LDLR.
(4) Upon uptake by the maternal liver, recently consumed VA can also be rapidly
re-secreted as retinol-RBP to be delivered to the placenta.
Maternal-Fetal Transfer of VA: Is There a Role for STRA6?
To validate the idea that retinol uptake is mediated by STRA6 (Kawaguchi et al. 2007;
Chen et al. 2016), several laboratories generated STRA6
−/− mice independently
using conventional gene knockout approaches (Terra et al. 2013; Amengual et al.
2014; Ruiz et al. 2012; Zemany et al. 2014). Surprisingly, STRA6
−/− mice are viable
and fertile when maintained on a regular chow diet and are born at a Mendelian
frequency (Terra et al. 2013; Amengual et al. 2014; Ruiz et al. 2012). However,
they display ocular malformations that are characteristic of VA-deficient animals.
Moreover, in young adult mutant mice maintained on a VA-deficient diet, the retinoid
content in the eye is dramatically reduced, and visual function is impaired (Terra
et al. 2013; Amengual et al. 2014; Ruiz et al. 2012). These data are consistent with
a mandatory role of the retinol-RBP-STRA6 pathway for retinoid delivery to the
eye, already evidenced by earlier studies in RBP
−/− mice (Quadro et al. 1999). The
embryonic development and, more generally, fertility of STRA6
−/− mice on a VAdeficient diet during pregnancy have never been investigated. Thus, to date, there
is no unequivocal proof of a role for STRA6 in the retinol-RBP transfer across
the placenta. We predict that, if STRA6 is critical for the retinol-RBP uptake at the
placental barrier, in the absence of dietary VA and of a functional retinol-RBP-STRA6
pathway, embryonic development should be severely hindered.
Maternal-Fetal Transfer of β-Carotene
β-carotene is the most abundant dietary VA precursor, constituting at least 30%
of the VA intake in industrialized countries and often serving as the sole source