CHOLINE DISTRIBUTION AND METABOLISM IN PREGNANT RATS AND FETUSES ARE INFLUENCED BY THE CHOLINE CONTENT OF THE MATERNAL DIET

Choline supplementation of pregnant rats between d 12 and 17 of pregna ncy permanently enhances the spatial memory of offspring; however, the mechanism is unknown. We examined the effect of choline supplementati on on metabolism of orally ingested choline by nonmated rats and pregn ant rats and their fetuses. We studied the metabolism of an acute oral dose of C-14-choline chloride in pregnant and nonmated rats with and without choline supplementation (25 mmol/L choline chloride in water) on d 12-17 of pregnancy. During the first 2 h after oral dosing, plasm a radiolabeled choline was detectable, whereas plasma choline metaboli tes contributed little to total radioactivity at any time. The pattern of accumulation of label in placentas was similar in all groups. Feta l tissues (i.e., brain, liver and carcass remnant) contained primarily C-14-phosphatidylcholine and C-14-phosphorylcholine. Also, we examine d the fetal tissue distribution of isotopically labeled (deuterated) c holine derived from the diet and from the dietary choline supplement. The distribution patterns for radiolabeled choline metabolites in fetu ses of supplemented darns accumulated significantly (P < 0.01) more of their total choline and its metabolites than fetuses of control darns during d 12-17 of gestation (50 vs. 20%). In fetuses from supplemente d darns, betaine concentrations were greater than in fetuses from cont rol darns in all organs assayed (by 36-57%). Phosphorylcholine concent rations in brain of fetuses from supplemented dams were also greater. These experiments identify potential metabolites of choline that might mediate the observed effects on brain development in the rats.