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Development of Sulfur Depletion in Pregnant and Fetal Rats: Interaction of Protein Restriction and Indole or Salicylamide Administration¹

Graduate School of Nutrition, Cornell University, Ithaca, New York 14850

In order to find the extent to which fetal development is affected by administration of compounds excreted as sulfoconjugates, interactions of protein restriction and drug administration have been studied in pregnant rats. Basal diets of 8% and 25% casein were fed alone and with indole (0.5%) and/or methionine (0.5%) supplementation. Addition of indole to a protein-restricted diet produced significant maternal growth retardation which was not alleviated by simultaneous methionine administration. Methionine supplementation did not induce greater indican formation but did exert a sparing action on body sulfur stores. Indole did not impair fetal growth during the late phase of gestation. Following intramuscular administration of ³⁵S-sulfate, a marked elevation was observed in the excretion of radiosulfate as indican by indole-fed rats, and in those animals, fetal and maternal liver retention of radiosulfate were reduced. In a subsequent study, 8% and 25% casein diets, with and without salicylamide supplementation (1.33%), were fed to pregnant rats. Salicylamide neither impaired maternal growth nor fetal development. The drug did, like indole, cause a significant reduction in the passage of radiosulfate to the fetus. The drug-induced reduction observed in fetal and placental retention and maternal liver and serum retention of radiosulfate corresponded to an increase in the fraction of the injected dose of radiosulfur that was excreted as ester sulfate. In both studies, retention of radiosulfate by the maternal liver and serum was independent of the stage of pregnancy, while the portion of the dose of radiosulfate transferred to the fetus increased with increasing fetal age. In the absence of drug administration, sulfate was taken up more avidly by maternal and fetal tissues with a limited sulfate supply. Results show that accretion of sulfate by the maturing rat fetus is depressed by foreign compounds excreted as sulfoconjugates.

KEY WORDS: • pregnancy • fetus • indole • salicylamide • sulfate

¹ Supported in part by funds provided through the State University of New York and Research Grant no. AM-12775 from the National Institute of Arthritis and Metabolic Diseases.

Manuscript received 18 January 1973.