β-Carotene supplementation decreases placental transcription of LDL receptor-related protein 1 in wild-type mice and stimulates placental β-carotene uptake in marginally vitamin A-deficient mice.

The human diet contains β-carotene as the most abundant precursor of vitamin A, an essential nutrient for embryogenesis. Our laboratory previously showed the importance of β-carotene metabolism via β-carotene-15,15'-oxygenase (CMOI) to support mouse embryonic development. However, the mechanisms regulating embryonic acquisition and utilization of β-carotene from the maternal circulation via placenta remain unknown. We used wild-type (WT) and Lrat(-/-)Rbp(-/-) (L(-/-)R(-/-)) mice, the latter being a model of marginal vitamin A deficiency. Pregnant dams, fed a nonpurified diet sufficient in vitamin A throughout life, were i.p. supplemented with β-carotene or vehicle at 13.5 d postcoitum (dpc). Effects of this acute maternal supplementation on retinoid and β-carotene metabolism in maternal (serum, liver) and developing tissues (placenta, yolk sac, embryo) were investigated at 14.5 dpc. We showed that, upon supplementation, placental β-carotene concentrations were greater in L(-/-)R(-/-) than in WT mice. However, the retinoid (retinol and retinyl ester) concentrations remained unchanged in placenta (and in all other tissues analyzed) of both genotypes upon β-carotene administration. We also showed that upon a single i.p. β-carotene supplementation, placental LDL receptor-related protein (Lrp1) mRNA expression was lower in WT mice, and embryonic CmoI mRNA expression was greater in L(-/-)R(-/-) mice. Together, these data suggest a potential role of LRP1 in mediating the uptake of β-carotene across the placenta and that even a marginally impaired maternal vitamin A status may influence uptake and utilization of β-carotene by the placenta and the embryo.