MATERNAL HYPERPHENYLALANINEMIA - EXPERIMENTAL-MODEL IN RATS

[Successful dietary treatment of children with classical phenylketonuria (PKU) has produced women of child-bearing age. When the PKU women become pregnant, usually many years after going off their low phenylalanine diets, they expose a population of fetuses who do not have the homozygous recessive PKU genes to hyperphenylalaninemia in utero. Reasons why maternal hyperphenylalaninemia cuases abnormal fetal development were studied in rats.] Experimental maternal hyperphenylalaninemia produced in pregnant F344 rats (Rattus norvegicus) by the combined use of p-chloro-DL-phenylalanine and L-phenylalanine reduced fetal birth weight in comparison to saline-injected controls. Offspring who experienced hyperphenylalaninemia in utero died within 5 days after birth. Fetal plasma phenylalanine levels were several times higher than maternal plasma phenylalanine levels, indicating that the placenta actively concentrates maternal phenylalaine. Fetal brain phenylalanine levels rose in direct proportion to elevations in fetal plasma phenylalanine, while maternal brain phenylalanine levels remained low during maternal plasma phenylalanine elevation; the contrast suggests that the maternal brain is better able than the fetal brain to screen itself against high circulating plasma phenylalanine levels.