Fetal Heart Malformations in Experimental Hyperphenylalaninemia in Pregnant Rats

Abstract Sprague-Dawley rats were given L-phenylalanine intraperitoneally from the 8th to 11th day of pregnancy. The hearts of the fetuses were examined on the 21st day of pregnancy. We found that the group given the higher doses of L-phenylalanine had significantly more heart defects than the group given the lower dose and the controls. Ventricular septal defect was found in 80 % of the fetuses with congenital deformities of the heart. [¹⁴C] Leucine uptake by the embryos was significantly lower in the group loaded with L-phenylalanine than in the controls.
The activity of thymidine kinase, one of the rate-limiting enzymes in DNA synthesis, was significantly lower in the brain and heart tissues of the young rats loaded with L-phenylalanine than in the controls.
Thus, when blood levels of phenylalanine are high in early pregnancy, an amino acid imbalance in the embryo occurs during fetal organogenesis. Also, thymidine kinase decreases, which may hinder DNA synthesis. Both of these mechanisms seem to be involved in the higher incidence of fetal heart malformations in maternal phenylketonuria.