Production of experimental models of foetal growth retardation by inhibition of DNA or protein synthesis.

Foetal growth retardation was induced in the rat by administration of hydroxyurea, an inhibitor of DNA synthesis, or cycloheximide, an inhibitor of protein synthesis. Each drug was given at 2 stages of pregnancy, either at 15 or at 18 days. Body and organ weights were studied at term (21 days) and DNA, RNA and protein estimations performed on brain and liver, with additional measurements of carbohydrate in the liver. Inhibition of DNA synthesis (hydroxyurea) caused reduction in organ cell population whether given early or late in pregnancy but the effect on the brain was more marked in early pregnancy. Haemopoietic cells in the liver were destroyed by repeated dosage on day 18. Inhibition of protein synthesis (cycloheximide) caused reduction in mean cell weight, but little reduction in cell population whether given early or late. With both drugs the effects on cell population were more severe with administration early in pregnancy. The results indicate that timing, mode of action and severity of stimulus are all important in determining the effect of any particular stress on foetal growth. The implications for studies on human intra-uterine growth retardation are discussed.