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The effects of phenylalanine on cultured rat embryos.

The offspring of mothers with untreated classic phenylketonuria (PKU) have shown a high frequency of microcephaly, mental retardation, pre- and postnatal growth retardation, and birth defects. The aim of this study was to determine whether phenylalanine (phe) is the teratogenic agent in maternal PKU. To observe the direct effects of phe on organogenesis, embryos of 9.5-day pregnant rats were cultured for 48 h in the presence of phe at concentrations of 0.1 to 6.0 mM. Within this range no morphological abnormalities occurred in exposed embryos, when compared to control embryos. However there was a reduction (P less than or equal to 0.05) in embryonic protein content and somite number at the highest concentration of phe (6.0 mM). This does not preclude the longer-term effects of phe at later stages of gestation. To examine phe transport into the embryo in response to elevated serum phe levels, 3H-phe uptake studies were undertaken. These showed that 3H-phe from the culture serum is incorporated rapidly into the free amino acid pools and embryonic protein. At serum concentrations of 1.4 mM or higher, phe saturation occurs in the cellular pools of the embryo. Amino acid analysis of the exocoelomic fluid showed that when embryos were cultured for 48 h in serum containing 3.45 mM phe, the total amino acid concentration was maintained near the control levels (16 mM). Of this, 27% (4.26 mM) was contributed by phe, and all other amino acids, except methionine, were decreased with respect to control levels.