2 Maternal-Fetal Transfer of Vitamin A …
33
are more sensitive than peripheral tissues to dietary VA restriction (Wallingford and
Underwood 1987).
The maternal intake of not only retinol and retinyl esters, but also retinoic acid
(RA), has been demonstrated to influence fetal retinoid levels. In rats, embryonic RA
levels were two times lower when multiple low teratogenic doses (6 mg of RA/kg of
body weight/day) were administered than when a single dose (same as above) was
given. However, in the maternal serum, RA levels were reduced nine-fold upon multiple maternal RA administrations (Collins et al. 1995). This discrepancy between
the embryonic (two-fold) and maternal (nine-fold) changes in serum RA levels suggested that placental regulatory mechanisms increase the transfer of retinoids to the
embryo when maternal circulating retinoid levels are lower (Collins et al. 1995).
The effect of maternal retinoid intake on fetal retinoid levels was also evaluated
in other species, leading to similar conclusions. Supplementation of pregnant goats
and sows with VA increased the VA levels in the fetal plasma and liver (Thomas
et al. 1947). The blood and liver VA levels of newborn lambs increased when ewes
were injected with retinol or retinyl palmitate, although only a small percentage of
the injected retinoids (0.37% of palmitate and 0.12% of retinol) was transferred to
the lamb liver (Mitchell et al. 1975). A much later study in rabbits evaluated the
effects of maternal retinoid intake on RA levels. Retinyl palmitate administration
from gestational days 7 to 12 only marginally increased maternal RA levels, but
caused embryonic levels of this VA metabolite to double (Tzimas et al. 1996).
Maternal VA Status and Fetal Retinoid Concentrations
VA status is defined by the concentration of retinol in the serum and the levels of
retinoids (VA and its derivatives) in the liver, the main retinoid storage site in the
body (Tanumihardjo et al. 2016). Dann (1934b) reported that VA stores in rat pups at
weaning roughly correlated with those of the maternal liver. However, other investigators noted that wide ranges of maternal hepatic VA stores corresponded to only
slight variations in newborn rat hepatic VA stores (Henry et al. 1949). Wallingford
and Underwood sought to determine the maternal VA status required to maintain
normal maternal and embryonic retinoid levels in rats. They found that a concentration of 3 μg VA (sum of retinol and retinyl esters)/g tissues in the maternal liver
was necessary to achieve normal retinoid levels in placentas, fetuses, and maternal
peripheral tissues (Wallingford and Underwood 1987).
In humans, measuring hepatic VA stores is not feasible without sophisticated
radioisotopic dilution techniques (Sheftel et al. 2018). Thus, measurements of serum
retinol levels are considered the gold standard for assessing the VA status in humans
(Quadro 2016). One human study demonstrated that maternal serum “carotene” levels correlated with newborn cord blood carotene and VA levels, while maternal serum
VA levels did not (Barnes 1951). Dimenstein and coworkers also examined the relationship between the maternal and newborn VA status in humans (Dimenstein et al.
33
are more sensitive than peripheral tissues to dietary VA restriction (Wallingford and
Underwood 1987).
The maternal intake of not only retinol and retinyl esters, but also retinoic acid
(RA), has been demonstrated to influence fetal retinoid levels. In rats, embryonic RA
levels were two times lower when multiple low teratogenic doses (6 mg of RA/kg of
body weight/day) were administered than when a single dose (same as above) was
given. However, in the maternal serum, RA levels were reduced nine-fold upon multiple maternal RA administrations (Collins et al. 1995). This discrepancy between
the embryonic (two-fold) and maternal (nine-fold) changes in serum RA levels suggested that placental regulatory mechanisms increase the transfer of retinoids to the
embryo when maternal circulating retinoid levels are lower (Collins et al. 1995).
The effect of maternal retinoid intake on fetal retinoid levels was also evaluated
in other species, leading to similar conclusions. Supplementation of pregnant goats
and sows with VA increased the VA levels in the fetal plasma and liver (Thomas
et al. 1947). The blood and liver VA levels of newborn lambs increased when ewes
were injected with retinol or retinyl palmitate, although only a small percentage of
the injected retinoids (0.37% of palmitate and 0.12% of retinol) was transferred to
the lamb liver (Mitchell et al. 1975). A much later study in rabbits evaluated the
effects of maternal retinoid intake on RA levels. Retinyl palmitate administration
from gestational days 7 to 12 only marginally increased maternal RA levels, but
caused embryonic levels of this VA metabolite to double (Tzimas et al. 1996).
Maternal VA Status and Fetal Retinoid Concentrations
VA status is defined by the concentration of retinol in the serum and the levels of
retinoids (VA and its derivatives) in the liver, the main retinoid storage site in the
body (Tanumihardjo et al. 2016). Dann (1934b) reported that VA stores in rat pups at
weaning roughly correlated with those of the maternal liver. However, other investigators noted that wide ranges of maternal hepatic VA stores corresponded to only
slight variations in newborn rat hepatic VA stores (Henry et al. 1949). Wallingford
and Underwood sought to determine the maternal VA status required to maintain
normal maternal and embryonic retinoid levels in rats. They found that a concentration of 3 μg VA (sum of retinol and retinyl esters)/g tissues in the maternal liver
was necessary to achieve normal retinoid levels in placentas, fetuses, and maternal
peripheral tissues (Wallingford and Underwood 1987).
In humans, measuring hepatic VA stores is not feasible without sophisticated
radioisotopic dilution techniques (Sheftel et al. 2018). Thus, measurements of serum
retinol levels are considered the gold standard for assessing the VA status in humans
(Quadro 2016). One human study demonstrated that maternal serum “carotene” levels correlated with newborn cord blood carotene and VA levels, while maternal serum
VA levels did not (Barnes 1951). Dimenstein and coworkers also examined the relationship between the maternal and newborn VA status in humans (Dimenstein et al.