Studies of the development of congenital anomalies in embryos of riboflavin-deficient, galactoflavin fed rats. I. Growth and embryologic pathology

Embryos from maternal rats maintained on a riboflavin‐deficient, galactoflavin‐augmented diet were compared by gross and histologic examinations with normal controls. On day 11 of gestation no differences were noted between control and treated embryos; on days 12 and 13 the treated embryos were smaller in overall size; and on day 14 the rate of differentiation of tissues of the treated embryos was delayed. The embryonic mortality occurred between day 11 and day 15. Serial sections of day‐14 treated embryos consistently contained extensive areas of necrosis in the mesoblast of the extremities and first branchial arch. A less frequent but similar lesion was found in the central nervous systems in two of four treated embryos examined on day 14. The pathologic lesion resembles the normal cell death which is part of the sculpturing process of developing extremities, but was of much greater magnitude. In addition, studies of sections of the extremities of the treated day‐14 embryos demonstrated a reduction in the number of cellular mitoses. By day 15 the necrosis had disappeared, the mode of clearing presumably being due to macrophage action as evidenced by photographs and by the presence of acid phosphatase‐containing cells in the areas of phagocytosis. In the early stages of mesenchymal condensation the treated specimens evidenced digital fusion but measurements of the relative total volume of mesenchyme were similar in treated and control specimens. Histochemical studies of the treated embryos but not the placentas or maternal tissues demonstrated an overall decrease in the reactions for succinic dehydrogenase from day 12 to day 17. Levels of malic and lactic dehydrogenases and alkaline and acid phosphatases were not decreased in the treated embryos when measured histochemically.