Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Physiologic and genomic analyses of nutrition-ethanol interactions during gestation: Implications for fetal ethanol toxicity. Exp Biol Med (Maywood) 2006 Sep;231(8):1379-97

Date

09/02/2006

Pubmed ID

16946407

DOI

10.1177/153537020623100812

Scopus ID

2-s2.0-33748316503   37 Citations

Abstract

Nutrition-ethanol (EtOH) interactions during gestation remain unclear primarily due to the lack of appropriate rodent models. In the present report we utilize total enteral nutrition (TEN) to specifically understand the roles of nutrition and caloric intake in EtOH-induced fetal toxicity. Time-impregnated rats were intragastrically fed either control or diets containing EtOH (8-14 g/kg/day) at a recommended caloric intake for pregnant rats or rats 30% undernourished, from gestation day (GD) 6-20. Decreased fetal weight and litter size (P < 0.05) and increased full litter resorptions (33% vs. 0%), were observed in undernourished dams compared to adequately fed rats given the same dose of EtOH, while undernutrition alone did not produce any fetal toxicity. Undernutrition led to impairment of EtOH metabolism, increased blood EtOH concentrations (160%), and decreased maternal hepatic ADH1 mRNA, protein, and activity. Microarray analyses of maternal hepatic gene expression on GD15 revealed that 369 genes were altered by EtOH in the presence of undernutrition, as compared to only 37 genes by EtOH per se (+/-2-fold, P < 0.05). Hierarchical clustering and gene ontology analysis revealed that stress and external stimulus responses, transcriptional regulation, cellular homeostasis, and protein metabolism were affected uniquely in the EtOH-under-nutrition group, but not by EtOH alone. Microarray data were confirmed using real-time RT-PCR. Undernourished EtOH-fed animals had 2-fold lower IGF-1 mRNA and 10-fold lower serum IGF-1 protein levels compared to undernourished controls (P < 0.0005). Examination of maternal GH signaling via STAT5a and -5b revealed significant reduction in both gene and protein expression produced by both EtOH and undernutrition. However, despite significantly elevated fetal BECs, fetal IGF-1 mRNA and protein were not affected by EtOH or EtOH-undernutrition combinations. Our data suggest that undernutrition potentiates the fetal toxicity of EtOH in part by disrupting maternal GH-IGF-1, signaling thereby decreasing maternal uterine capacity and placental growth.

Author List

Shankar K, Hidestrand M, Liu X, Xiao R, Skinner CM, Simmen FA, Badger TM, Ronis MJ

Author

Mats Hidestrand PhD Adjunct Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alcohol Dehydrogenase
Aldehyde Dehydrogenase
Animals
Blotting, Western
Cytochrome P-450 CYP2E1
Dose-Response Relationship, Drug
Enteral Nutrition
Ethanol
Female
Fetal Alcohol Spectrum Disorders
Fetus
Gene Expression
Insulin-Like Growth Factor I
Liver
Malnutrition
Oligonucleotide Array Sequence Analysis
Pregnancy
Prenatal Exposure Delayed Effects
Prenatal Nutritional Physiological Phenomena
RNA, Messenger
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75