PEDIATRICS Vol. 23 No. 1 January 1959, pp. 245-251
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INHERITANCE OF SUSCEPTIBILITY TO CONGENITAL DEFORMITY

Metabolic Clues Provided by Experiments with Teratogenic Agents

Meredith N. Runner Ph.D.1

1 Roscoe B. Jackson Memorial Laboratory

Fasting for 24 hours during the ninth day of pregnancy resulted in 22% of the fetuses having either cranioschisis or deformed ribs or both at 18 days post coitum. The fasting treatment affected neither the frequency of pregnancies following matings nor the incidence of prenatal mortality.

Fetuses were protected from the fasting effect by relatively small quantities of a variety of nutrients, i.e., glucose, ketone-body or amino acids administered by stomach tube during the fasting period. The array of protective compounds suggested that they acted by supplying substrate for the citric acid cycle.

Four teratogenic treatments (insulin, iodoacetate, x-methylfolic acid and fasting) produced similar abnormalities of development. A metabolic scheme is presented to suggest that each of these agents may interfere with reactions in the citric acid cycle.

Administration of nutrients during the fasting period and use of teratogenic agents have provided circumstantial evidence that carbohydrate metabolism may be selectively critical for morphogenesis of embryonic neural tube and for differentiation of precartilaginous mesenchyme.