Submitted to: Pharmacological Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2002
Publication Date: 3/1/2003
Citation: Ren, J., Roughead, Z.K., Wold. L.E., Norby, F.L., Rakoczy, S., Mabey, R.L., Brown-Borg, H.M. Increases in insulin-like growth factor-1 and peroxidative damage after gestational ethanol exposure in rats. Pharmacological Research. 2003. v.47.p. 341-347. Interpretive Summary: The devastating effects of alcohol (ethanol) consumption during pregnancy on the fetus have been widely documented, however, few reports have addressed the impact on the maternal tissues. We designed this study to examine the influence of ethanol exposure during pregnancy on maternal organs by measuring postpartum oxidative damage and the concentrations of insulin-like growth factor-1 (IGF-1). This peptide hormone (IGF-1) has many functions including antioxidant capabilities. Pregnant female rats were fed from day 2 of gestation until labor with control or ethanol liquid diets and were sacrificed 6 weeks after giving birth. We found that litter size was significantly less for ethanol-fed dams and fewer pups survived in this group (57.1% vs 97.8% in the control group). The amount of IGF-1 in the liver and kidney were higher in the ethanol-fed mothers. Also, we found more oxidative damage in the liver as measured by the amount of oxidized fat and protein byproducts called 4-hydroxynonemal and protein carbonyls. The levels of another antioxidant system (glutathione) were not different between the ethanol-fed and control dams. Collectively, these data suggest that gestational ethanol exposure causes oxidative damage to vital organs (such as the liver) despite compensatory increases in organ IGF-1 levels.
Technical Abstract: Ethanol exposure during pregnancy elicits profound detrimental developmental and behavioral effects such as reduced levels of insulin-like growth factor-1 (IGF-1) in the fetus. However, few reports have addressed its impact on postpartum dams. This study was designed to examine the influence of gestational ethanol exposure on postpartum maternal organ oxidative damage and IGF-1 level. Pregnant female rats were pair-fed from day 2 of gestation until labor with control or ethanol (6.36% v/v) liquid diets and were sacrificed 6 weeks after parturition (ethanol withdrawn after parturition). Litter size was significantly less for ethanol-fed dams. One-week postnatal pup survival was significantly lower in the ethanol-fed (57.2%) than the control (97.8%) group. Liver and kidney tissues IGF-1 levels and mRNA were elevated in the ethanol-fed mothers, accompanied by hepatic but not renal oxidative damage, indicated by profound lipid peroxidation (measured by malondialdehyde and 4-hydroxynonemal) and protein carbonyl formation. The levels of reduced glutathione (GSH), oxidized gluthathione (GSSG) and GSH/GSSG ratio were not different between the ethanol-fed and control dams. Collectively, these data suggest that gestational ethanol exposure may lead to postpartum oxidative organ damage and a possible compensatory increase in organ IGF-1 levels.