USE OF INTRAUTERINE MICRODIALYSIS TO INVESTIGATE METHANOL-INDUCED ALTERATIONS IN UTEROPLACENTAL BLOOD-FLOW

Methanol is teratogenic in rodents; it has been postulated that this t eratogenicity may be mediated in part by conceptal hypoxia. To constru ct a model to predict conceptal risk following maternal methanol expos ure, conceptal disposition of methanol must be determined and any effe cts of such exposure on blood how must be quantitated. In the present study, these toxicokinetic and toxicodynamic parameters were evaluated by in vivo intrauterine microdialysis. Microdialysis probes were inse rted into the uteri of Gestational Day (gd) 20 rats; methanol was admi nistered as either an iv bolus (100 or 500 mg/kg) or infusion (100 or 1000 mg/kg/hr). In separate experiments, methanol (100 or 500 mg/kg) a nd (H2O)-H-3 (20 mu Ci/kg) were administered iv to gd 20 and 14 rats a nd gd 18 mice. In both experiments, maternal blood and uterine microdi alysate were collected and analyzed for methanol or (H2O)-H-3 content. The methanol concentration-time data were consistent with saturable m aternal elimination and apparent first-order transfer between maternal and conceptal compartments; at distribution equilibrium, conceptal me thanol concentrations exceeded those in the dam by approximately 25%, The initial rate of conceptal permeation of methanol was proportional to the reciprocal of maternal blood methanol concentration (r(2) = 0.9 10). Methanol also reduced significantly the rate of (H2O)-H-3 uptake into the conceptus in a concentration-dependent fashion in gd 14 and 2 0 rats and gd 18 mice. These data indicate that methanol may decrease uteroplacental blood flow, decreasing methanol presentation to the con ceptus and possibly producing conceptal hypoxia. (C) 1996 Academic Pre ss, Inc.