Maternal chronic vitamin A toxicity amplifies early fetal liver retinyl ester storage in captive Old World monkeys

Abstract

Excessive preformed vitamin A (VA) intake is contraindicated during pregnancy due to teratogenic concerns. Recent studies have provided biochemical and histological evidence of chronic VA toxicity in captive Old World monkeys consuming laboratory diets containing high concentrations of retinyl acetate. This study investigated the effects of maternal chronic VA toxicity on early fetal hepatic VA storage. Monkey fetal livers (n = 19) ranging from 35 to 93 d gestational age (mid 1st to late 2nd trimester) were analyzed for VA content. Retinoic acid was quantified in a subset of livers (n = 9). Retinyl esters were identified in all fetal livers, and retinol, as a percentage, was more pronounced in younger fetuses. Hepatic VA concentration increased with gestational age (r = 0.92, P < 0.0001), ranging from 0.0011 μ mol/g in the youngest fetus (35 d) to 0.26 μ mol/g in the oldest fetus (93 d) indicating linear accumulation. Mean hepatic VA concentrations were 0.023 ± 0.008 μmol/g for the 1st trimester and 0.19 ± 0.06 μmol/g for the 2nd trimester. Hepatic VA concentrations from 2nd trimester fetuses were higher than those observed in fetal human and monkey livers from later stages of development, when growth and VA accumulation rates are assumed to be the highest. Maternal VA toxicity from excessive intake results in amplified early fetal hepatic retinyl ester storage. Supported by NIH-NIDDK RO1-61973 and 5P51 RR 000167.