Impaired glucose homeostasis during postimplantation pregnancy in the mouse following acute exposure to ethanol, with particular reference to the uterus and embryo.
Dramatic changes in the levels of plasma glucose and lactate and liver glycogen were observed in mice, given an intraperitoneal injection of ethanol (3.5 g/kg body weight) on Day 9 of pregnancy, during the period of time (6 h) required to clear the drug from the circulatory system. These alterations were accompanied by significant changes in the rates of accumulation of some glycolytic and citric acid cycle intermediates in the uterus, including glucose-6-phosphate, fructose-6-phosphate, lactate, citrate, alpha-ketoglutarate, and succinate. Although the changes in some metabolic parameters were very transient, not all metabolites returned to control values by the time that the drug had been cleared from the maternal system. Alcohol also impaired the capacity of Day 9 mouse embryos to metabolize [14C]glucose under culture conditions in vitro and significantly increased the amount of the aldohexose accumulating in the fetal membrane fluid when administered on Day 14 of pregnancy. However, ethanol neither influenced the ratio of NADH to NAD+ in the uterus nor changed the glycolytic and respiratory activity of the uterine endometrium when coincubated with the tissue in vitro. The results indicate that glucose homeostasis is impaired in both the embryo and the maternal system of mice acutely exposed to alcohol during the teratogenically sensitive period of postimplantation pregnancy and support the thesis that this phenomenon may present an important mechanism underlying the embryo-toxic effects of alcohol consumed under "binge" drinking conditions during pregnancy. However, the results also suggest that the effects registered at the uterine level most likely involve stress reactions and acetate rather than primary actions of the drug on the organ.
Murdoch
R N
RN
Department of Biological Sciences, University of Newcastle, New South Wales, Australia.
Simm
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006600:Hexosephosphates / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007700:Kinetics; D007773:Lactates / Q000097:blood / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D002951:Citrates; D006600:Hexosephosphates; D007773:Lactates; D019343:Citric Acid; D019344:Lactic Acid; D000431:Ethanol; D006003:Glycogen; D005947:Glucose