Reduction of all-trans-retinoic acid–induced teratogenesis in the rat by glycine administration

Abstract

Prenatal rat embryo exposure to retinoids induces severe malformations in various organs; the most active and teratogenic metabolite is all-trans-retinoic acid (atRA). The mechanisms of this embryopathy are only partly known. In the present study, the influence of glycine on the teratogenicity of atRA was investigated. Embryos from 5 groups of white rats were studied: Group 1 remained untreated; Group 2 received glycine 2% in drinking water ad libitum from the first gestational day (GD 1); Group 3 was administered vehicle (corn oil); Group 4 was treated with atRA (50 mg/kg of body weight) injected (IP); and Group 5 was treated with atRA (50 mg/kg of body weight IP) plus glycine 2% in drinking water ad libitum from GD 1. atRA was administrated daily from GD 8-10. Dams were killed on the 21st day of pregnancy, and their fetuses were examined to detect external, visceral, and skeletal malformations. The results show that the atRA-administered dose is not toxic for the dams, and that although fetal death was not observed, it produced abnormalities in the fetuses. Glycine reduced atRA-induced teratogenic effects (external and skeletal defects). The results indicate that glycine effectively reduces the teratogenic effects of atRA. Thus, glycine might be useful for the prevention of vitamin A teratogenicity.