Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Few studies have examined the underlying mechanism(s) of action of ethanol (EtOH) in the developing fetus, especially for non-alcoholic drinking patterns. We have established an experimental protocol using the conscious instrumented near-term pregnant ewe, in which the EtOH-induced suppression of fetal breathing movements (FBM), observed in pregnant women, can be mimicked. The goal of this thesis research was to further characterize the effects of EtOH on the fetus and to elucidate the underlying mechanism(s) of EtOH action, specifically as it pertains to the suppression of FBM.;A previous study by this laboratory demonstrated that maternal intravenous infusion of EtOH (1 g/kg maternal body weight (MBW)/1 h), to near-term pregnant ewes, resulted in the suppression of FBM for 9 h, and fetal brain (electrocortical (ECoG)) activity and eye (electroocular (EOG)) activity for 3 h. Once-daily 1 h maternal EtOH (1 g/kg MBW) administration for seven or fourteen days resulted in the development of tolerance to some of the fetal effects of EtOH. By seven days, maternal EtOH infusion had no effect on fetal ECoG activity or EOG activity, and by fourteen days, maternal EtOH infusion had no significant effect on the incidence of FBM. This development of tolerance was functional and not dispositional, as there was no change in the pharmacokinetics of EtOH in the maternal-fetal unit.;Maternal administration of high dose EtOH (3 g/kg MBW over 8 h), the equivalent of a binge-type drinking episode, had no significant effect on maternal and fetal blood gases and acid-base balance. This suggests that during near-term ovine pregnancy, hypoxemia is not involved in the acute fetal effects of EtOH.;Maternal administration of EtOH (1 g/kg MBW) produced a significant elevation in maternal and fetal arterial plasma prostaglandin E{dollar}\sb2{dollar} (PGE{dollar}\sb2{dollar}) concentrations which were positively correlated with the respective blood EtOH concentrations. Fetal cerebrospinal fluid (CSF) PGE{dollar}\sb2{dollar} concentration also was elevated. Fetal plasma and CSF PGE{dollar}\sb2{dollar} concentrations were positively correlated and were both negatively correlated with the incidence of FBM following EtOH administration. Fetal plasma PGE{dollar}\sb2{dollar} concentration also was correlated with the incidence of FBM during control periods. Fetal treatment with indomethacin (1 and 2 mg/kg fetal body weight/h) antagonized the EtOH-induced suppression of FBM but did not antagonize the EtOH-induced suppression of fetal ECoG or EOG activity. This effect of indomethacin appeared to be due to its effect to decrease fetal PGE{dollar}\sb2{dollar} concentration.;The results of this thesis have further characterized the effects of EtOH on the near-term ovine fetus and have provided evidence that suggests that prostaglandins, particularly PGE{dollar}\sb2{dollar}, may be involved in both the EtOH-induced suppression of FBM and the normal control of FBM in the ovine fetus.



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