Early biochemical changes in the embryonic rat heart after teratogen treatment

The effects on mucopolysaccharide synthesis in isolated embryonic rat hearts of in vivo and/or in vitro 6‐aminonicotinamide, dietary‐induced folic acid deficiency, aminopterin, and trypan blue were investigated using uptake of 35S‐sodium sulfate to measure the rate of mucopolysaccharide synthesis. Intraperitoneal injection of 6‐aminonicotinamide on day 11 of gestation caused inhibition of mucopolysaccharide synthesis which was most pronounced at day 13. A similar effect followed in vitro 6‐aminonicotinamide treatment. Maternal folic acid deficiency on days 9–11 of pregnancy caused decreased mucopolysaccharide synthesis in embryonic hearts at day 14. In vitro treatment with the folic acid antagonist aminopterin inhibited the rate of synthesis on days 13–16. In vivo trypan blue on day 9 of pregnancy had no effect on the rate of mucopolysaccharide synthesis. However, in vitro trypan blue treatment of embryonic hearts resulted in a marked depression in synthetic rate. Aminopterin and 6‐aminonicotinamide had no noticeable effect on the rate of protein synthesis in isolated embryonic hearts as determined by measurement of 3H‐leucine incorporation. Thus mucopolysaccharide synthesis in isolated embryonic rat hearts was susceptible to the action of the teratogens used. It is postulated that these teratogens act by blocking a biochemical reaction in the synthesis of mucopolysaccharides and are not affecting the cellular machinery necessary for general protein synthesis.