Effects of nitrous oxide on maternal and embryonic folate metabolism in rats

Deficiency of the vitamin, folic acid, or exposure to the anesthetic gas, nitrous oxide (N2O), has been reported to be teratogenic in rats. N2O oxidizes the vitamin B12 prosthetic group of methionine synthetase. This enzyme converts the plasma folate form, 5-methyltetrahydrofolate, to tetrahydrofolate and catalyzes the methylation of homocysteine to methionine. To assess the effects of N2O on folate levels in embryos, pregnant rats were exposed to a mixture of 50% N2O:50% O2 for 4, 24 or 48 h. Animals were sacrificed on day 14 of gestation immediately following treatment. Exposure to N2O was not acutely embryotoxic. It significantly inhibited methionine synthetase activity in maternal liver as well as embryonic tissue. Exposure to N2O for 48 h led to a loss of folates from liver and embryos and marked changes in the distribution of folates within these tissues. Specifically, the levels of nonmethylated folates including tetrahydrofolate in embryonic tissue were reduced by 50%, a loss which could be very significant in regard to embryonic macromolecular synthesis.