36
L. Quadro and E. K. Spiegler
1987) postulated that both the yolk sac and the fetus could synthesize RBP and TTR
for retinol transport. However, in mice, RBP mRNA and protein were not detected in
the chorioallantoic placenta, but were detected in the visceral endoderm of the yolk
sac placenta (Johansson et al. 1997). The placental transfer of maternal RBP in mice
was ultimately refuted by Quadro et al. (2004a, b). It is worth noting that VA was
eventually reported to flow bidirectionally across the placenta in a “dynamic steadystate relationship” in rats (Ismadi and Olson 1982) as well as in lambs (Donoghue
et al. 1982).
Maternal-Fetal Transfer of VA: The Role for Other Placental
Proteins
On the heels of the debate over the involvement of RBP and TTR in the placental
transfer of retinol, several studies explored the expression of other placental genes.
Bouillet et al. (1997) detected Stra6 expression in mice in the primitive placenta,
chorioallantoic placenta and labyrinthine region of the placenta (where maternal and
fetal blood are exchanged). Later, Sapin et al. (2000) reported that, during early
placentation in mouse, Stra6 was expressed in the endometrial/decidual cells, ectoplacental cone/chorion and yolk sac. However, not until 2007 was STRA6 confirmed
to be the cell-surface retinol: RBP receptor by Kawaguchi et al. (2007). This finding
energized the field, since it appeared to confirm a long-held “alternative retinol transfer” hypothesis that retinol is taken up by a cell-surface receptor for retinol: RBP and
then esterified and released into the fetal circulation (Torma and Vahlquist 1986).
CRBPI (a potential cofactor of STRA6) (Noy 2016) was also detected in the
trophoblast cells of the mouse placental labyrinth, as well as in the visceral endoderm
of the yolk sac (Johansson et al. 1997). These results, combined with the observation
that radiolabeled retinoids accumulated in the visceral yolk sac endodermal cells,
led Johansson et al. (1997) to conclude that the visceral yolk sac, rather than the
chorioallantoic placenta, transfers retinoids to the mouse embryo. It should be noted
that the placental localization of binding proteins and enzymes involved in retinoid
biology has never been systematically analyzed, so the discrepancies among the
above studies remain unresolved.
Maternal-Fetal Transfer of Other Retinoids
In the 1980s, attention became focused on the placenta’s permeability to various
forms of RA, in part fueled by the discovery that 13-cis RA (isotretinoin) was teratogenic. In hamsters, all-trans RA, 13-cis RA, all-trans-4-oxo RA, 9-cis-retinal
and all-trans-retinyl acetate administered orally were reported to cross the placenta
towards the fetus (Howard et al. 1989). High doses of 13-cis RA were also transferred
L. Quadro and E. K. Spiegler
1987) postulated that both the yolk sac and the fetus could synthesize RBP and TTR
for retinol transport. However, in mice, RBP mRNA and protein were not detected in
the chorioallantoic placenta, but were detected in the visceral endoderm of the yolk
sac placenta (Johansson et al. 1997). The placental transfer of maternal RBP in mice
was ultimately refuted by Quadro et al. (2004a, b). It is worth noting that VA was
eventually reported to flow bidirectionally across the placenta in a “dynamic steadystate relationship” in rats (Ismadi and Olson 1982) as well as in lambs (Donoghue
et al. 1982).
Maternal-Fetal Transfer of VA: The Role for Other Placental
Proteins
On the heels of the debate over the involvement of RBP and TTR in the placental
transfer of retinol, several studies explored the expression of other placental genes.
Bouillet et al. (1997) detected Stra6 expression in mice in the primitive placenta,
chorioallantoic placenta and labyrinthine region of the placenta (where maternal and
fetal blood are exchanged). Later, Sapin et al. (2000) reported that, during early
placentation in mouse, Stra6 was expressed in the endometrial/decidual cells, ectoplacental cone/chorion and yolk sac. However, not until 2007 was STRA6 confirmed
to be the cell-surface retinol: RBP receptor by Kawaguchi et al. (2007). This finding
energized the field, since it appeared to confirm a long-held “alternative retinol transfer” hypothesis that retinol is taken up by a cell-surface receptor for retinol: RBP and
then esterified and released into the fetal circulation (Torma and Vahlquist 1986).
CRBPI (a potential cofactor of STRA6) (Noy 2016) was also detected in the
trophoblast cells of the mouse placental labyrinth, as well as in the visceral endoderm
of the yolk sac (Johansson et al. 1997). These results, combined with the observation
that radiolabeled retinoids accumulated in the visceral yolk sac endodermal cells,
led Johansson et al. (1997) to conclude that the visceral yolk sac, rather than the
chorioallantoic placenta, transfers retinoids to the mouse embryo. It should be noted
that the placental localization of binding proteins and enzymes involved in retinoid
biology has never been systematically analyzed, so the discrepancies among the
above studies remain unresolved.
Maternal-Fetal Transfer of Other Retinoids
In the 1980s, attention became focused on the placenta’s permeability to various
forms of RA, in part fueled by the discovery that 13-cis RA (isotretinoin) was teratogenic. In hamsters, all-trans RA, 13-cis RA, all-trans-4-oxo RA, 9-cis-retinal
and all-trans-retinyl acetate administered orally were reported to cross the placenta
towards the fetus (Howard et al. 1989). High doses of 13-cis RA were also transferred