Ornithine decarboxylase activity and polyamine concentrations in fetal rat brain: response to chronic hypoxic-hypoxia and/or carbon monoxide-hypoxia

Abstract

Ornithine decarboxylase activity (ODC; E.C. 4.1.1.17), is significantly elevated in fetal and newborn rat brain in response to acute hypoxia. Because relatively little is known about ODC activities and polyamine metabolism in hypoxia and also because ODC and the polyamines are essential for normal growth and development, we examined the effect of chronic maternal hypoxic-hypoxia (16-10.5% O 2), carbon monoxide-hypoxia (100–200 ppm CO) and their combination, on fetal weight, fetal brain ODC activity and polyamine concentrations. Time-dated pregnant Sprague-Dawley rats were chronically exposed to hypoxia from gestational day 15 (E-15), to gestational day 21 (E-21), in individual chambers. Pair-fed controls were given an amount equivalent to that eaten by a hypoxic dam over the previous 24 h. We measured fetal weight, as well as brain ODC activity and polyamine concentrations on both E-19 and E-21. Pair-feeding had no effect on fetal weight, ODC activity or polyamine concentrations. On both E-19 and E-21, however, fetal weights were significantly reduced with higher levels of hypoxic-hypoxia (e.g., 10.5% O 2). At 100 or 200 ppm, carbon monoxide alone appeared not to affect fetal weight; however, combined with even mild hypoxia (16% O 2), fetal weights were reduced almost 20%, suggesting that together, CO- and hypoxic-hypoxia exert a synergistic effect on fetal weight decrements. (1) There was no consistent pattern of ODC activity changes which correlated to the fetal weight losses or levels of hypoxia. These results suggest that ODC activity may not be a good marker for chronic, as opposed to acute hypoxia. (2) Whole brain polyamine concentrations were markedly affected by relatively mild chronic hypoxia (16% O 2), with or without CO. Severe chronic hypoxia did not appear to affect brain polyamine levels, but dramatically affected fetal weight. (3) Our present findings vis á vis the fetal weight losses may be of clinical relevance to pregnant women living at higher altitudes who smoke or are exposed to higher levels of environmental carbon monoxide.