2 Maternal-Fetal Transfer of Vitamin A …
37
across the placenta in rabbits (Eckhoff et al. 1994). However, in mice (Kraft et al.
1987; Creech Kraft et al. 1989) and rats (Collins et al. 1994), the placental transfer
of 13-cis RA was far lower than that of all-trans RA, at either high or low doses.
Moreover, the placental transfer of 13-cis and all-trans RA glucuronides was more
efficient at later gestational stages than at earlier stages, and at certain concentrations, the same was observed for 13-cis RA (Tzimas et al. 1995). In rats, the placental
transport of RA was lower than that of retinyl acetate, which was thought to explain
the inefficiency of RA for fetal growth (Shukla et al. 1986).
Although much attention was given to RA in the above studies and in most of the
developmental studies thereafter, a small number of studies indicated that this VA
derivative is not the only one required in proper doses for normal embryonic development. Indeed, Thompson et al. (1964) found that, in rats, RA could restore growth,
but not vision or successful pregnancies. In fact, retinol is required for offspring to be
obtained. Further studies by this group (Howell et al. 1964) showed that the placentas
of retinol-deprived rats exhibited signs of necrosis at gestational days 15–16, beginning in the junctional zone and spreading to the labyrinth over time. Three decades
later, Wellick and DeLuca (Wellik and DeLuca 1995) also demonstrated that RAsupplemented, VA-deficient pregnant rats resorbed their fetuses unless supplemented
with retinol by 10 dpc.
Maternal-Fetal Transfer of VA—Unanswered Questions
A few studies in the 1980s and 1990s marked a shift away from the developmental
view and toward the metabolic perspective on gestational VA metabolism. Ismadi
and Olson (Ismadi and Olson 1982) reported an increase in the total VA content
of rat placentas at the end of pregnancy (15–21 days). Later, Satre and colleagues
(1992) charted the retinol, retinyl ester and RA levels in maternal serum, embryos
and placentas of mice from mid to late gestation. In placenta, retinol and retinyl
ester levels declined somewhat from gestational days 13 to 16, but were overall
relatively constant. In contrast, embryonic retinol levels began eight-fold lower than
placental retinol levels on day 10 and became four-fold greater by day 14. In the
conceptus as a whole, the VA content quintupled from days 10 to 14. Meanwhile,
maternal plasma retinol levels declined sharply from gestational days 8 to 13 (which
the authors attributed to the higher embryonic demands during organogenesis), and
gradually returned to non-pregnant levels during the remainder of the pregnancy,
whereas maternal serum retinyl ester levels did not change. Two remarks in this
paper by Satre and colleagues (1992) are worth repeating:
(1) “Neither the precise manner nor the extent to which the placenta functions to
regulate the transfer of VA to the developing embryo is known.”
(2) “The extent to which the extra-embryonic tissues function as storage sites
and/or control the rate of transfer to the embryo at any time during gestation is
[also]…unknown.”
37
across the placenta in rabbits (Eckhoff et al. 1994). However, in mice (Kraft et al.
1987; Creech Kraft et al. 1989) and rats (Collins et al. 1994), the placental transfer
of 13-cis RA was far lower than that of all-trans RA, at either high or low doses.
Moreover, the placental transfer of 13-cis and all-trans RA glucuronides was more
efficient at later gestational stages than at earlier stages, and at certain concentrations, the same was observed for 13-cis RA (Tzimas et al. 1995). In rats, the placental
transport of RA was lower than that of retinyl acetate, which was thought to explain
the inefficiency of RA for fetal growth (Shukla et al. 1986).
Although much attention was given to RA in the above studies and in most of the
developmental studies thereafter, a small number of studies indicated that this VA
derivative is not the only one required in proper doses for normal embryonic development. Indeed, Thompson et al. (1964) found that, in rats, RA could restore growth,
but not vision or successful pregnancies. In fact, retinol is required for offspring to be
obtained. Further studies by this group (Howell et al. 1964) showed that the placentas
of retinol-deprived rats exhibited signs of necrosis at gestational days 15–16, beginning in the junctional zone and spreading to the labyrinth over time. Three decades
later, Wellick and DeLuca (Wellik and DeLuca 1995) also demonstrated that RAsupplemented, VA-deficient pregnant rats resorbed their fetuses unless supplemented
with retinol by 10 dpc.
Maternal-Fetal Transfer of VA—Unanswered Questions
A few studies in the 1980s and 1990s marked a shift away from the developmental
view and toward the metabolic perspective on gestational VA metabolism. Ismadi
and Olson (Ismadi and Olson 1982) reported an increase in the total VA content
of rat placentas at the end of pregnancy (15–21 days). Later, Satre and colleagues
(1992) charted the retinol, retinyl ester and RA levels in maternal serum, embryos
and placentas of mice from mid to late gestation. In placenta, retinol and retinyl
ester levels declined somewhat from gestational days 13 to 16, but were overall
relatively constant. In contrast, embryonic retinol levels began eight-fold lower than
placental retinol levels on day 10 and became four-fold greater by day 14. In the
conceptus as a whole, the VA content quintupled from days 10 to 14. Meanwhile,
maternal plasma retinol levels declined sharply from gestational days 8 to 13 (which
the authors attributed to the higher embryonic demands during organogenesis), and
gradually returned to non-pregnant levels during the remainder of the pregnancy,
whereas maternal serum retinyl ester levels did not change. Two remarks in this
paper by Satre and colleagues (1992) are worth repeating:
(1) “Neither the precise manner nor the extent to which the placenta functions to
regulate the transfer of VA to the developing embryo is known.”
(2) “The extent to which the extra-embryonic tissues function as storage sites
and/or control the rate of transfer to the embryo at any time during gestation is
[also]…unknown.”