A rodent model of low- to moderate-dose ethanol consumption during pregnancy: patterns of ethanol consumption and effects on fetal and offspring growth.
It is unknown whether low to moderate maternal alcohol consumption adversely affects postnatal health. The aim of the present study was to develop a rodent model of low-moderate-dose prenatal ethanol (EtOH) exposure. Sprague-Dawley rats were fed a liquid diet with or without 6% v/v EtOH throughout gestation and the pattern of dietary consumption determined. Fetal bodyweights and hepatic alcohol-metabolising gene expression were measured on embryonic Day (E) 20 and offspring growth studied until 1 year. At E8 the plasma EtOH concentration was 0.03%. There was little difference in dietary consumption between the two treatment groups. At E20, EtOH-exposed fetuses were significantly lighter than controls and had significantly decreased ADH4 and increased CYP2E1 gene expression. Offspring killed on postnatal Day (PN) 30 did not exhibit any growth deficits. Longitudinal repeated measures of offspring growth demonstrated slower growth in males from EtOH-fed dams between 7 and 12 months of age; a cohort of male pups killed at 8 months of age had a reduced crown-rump length and kidney weight. In conclusion, a liquid diet of 6% v/v EtOH fed to pregnant dams throughout gestation caused a 3-8% reduction in fetal growth and brain sparing, with growth differences observed in male offspring later in life. This model will be useful for future studies on the effects of low-moderate EtOH on the developmental origins of health and disease.
School of Biomedical Sciences, The University of Queensland, St Lucia, Qld 4072, Australia. m.probyn@uq.edu.au
Megan E
ME
Probyn
Simone
S
Zanini
Leigh C
LC
Ward
John F
JF
Bertram
Karen M
KM
Moritz
D000367:Age Factors; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D049628:Body Size / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005865:Gestational Age; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012741:Sexual Maturation / Q000187:drug effects
D012333:RNA, Messenger; D000431:Ethanol; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; D019392:Cytochrome P-450 CYP2E1