Embryotoxicity of methanol in well-nourished and malnourished rats

1. The objective of the present study was to investigate whether maternal protein-energy malnutrition alters methanol-induced embryotoxic effects in rats. 2. On day 0 of pregnancy, dams were assigned at random to one of the following treatment groups: well-nourished methanol (WNM), well-nourished control (WNC), malnourished methanol (MNM) and malnourished control (MNC). Malnourished animals received half of the well-nourished food intake (ca 12 g/day) throughout pregnancy. Methanol was administered by gavage (2.5 g/kg body weight) from gestation day 6 to 15. 3. Rats were weighed on days 0, 6 to 15, and 21 of pregnancy. On day 21 rats were submitted to cesarean section. The number of implantations, living and dead fetuses, resorptions and corpora lutea was recorded. All fetuses were weighed, examined for externally visible malformations, fixed, and examined for skeletal anomalies after clearing and staining with Alizarin Red S. 4. An increased proportion of fetuses with skeletal malformations, particularly cervical extra ribs, was found in the methanol-treated groups (fetuses with skeletal malformations: WNC = 5.6%, WNM = 45.4%, MNC = 3.8%, and MNM = 38.8%). Malnutrition produced fetal growth retardation, but did not cause any increase in the occurrence of gross structural malformations. The methanol-induced increase in the proportion of fetuses with extra ribs was not altered by malnutrition, but methanol potentiated the malnutrition-induced increase in the proportion of fetuses with signs of delayed ossification (WNC = 18.6%, WNM = 25.4%, MNC = 39.7%, and MNM = 78.4%). 5. These findings suggest that methanol-induced gross structural malformations are not affected by maternal malnutrition, but the delay in ossification caused by malnutrition is aggravated by treatment with methanol.