CHARACTERIZATION OF CHOLINE METABOLISM AND SECRETION BY HUMAN PLACENTAL TROPHOBLASTS IN CULTURE

Choline is an essential nutrient for fetal development and may be util ized to form phospholipids such as phosphatidylcholine and sphingomyel in; to synthesize the neurotransmitter, acetylcholine; and to donate m ethyl groups after being oxidized to betaine. Since the majority of ch oline required for fetal growth must be transported by the placenta fr om the maternal circulation, we examined the ability of isolated human trophoblasts to metabolize choline and to release choline and its met abolites into culture medium. Cytotrophoblasts were isolated from norm al, full-term human placentas and incubated with [C-14]choline for 3 h ; the cells were washed to remove extracellular radiolabel, and the ch anges in intracellular and medium choline pools were followed for an a dditional 24 h. During the incubation, choline rapidly reached steady state intracellularly and label was incorporated into betaine, phospho choline, cytidylyldiphosphocholine, phosphatidylcholine, glycerophosph ocholine, lysophosphatidylcholine, and sphingomyelin. All labeled chol ine metabolites in cells, except glycerophosphocholine, decreased at 6 and 27 h of incubation (3 and 24 h, respectively, after labeled choli ne was removed), and labeled metabolites appeared in media. By 24 h af ter labeled choline was removed, the major labeled metabolites in the media were choline (82%), betaine (11%), and glycerophosphocholine (5% ). Small amounts of phosphatidylcholine (1%), and lysophosphatidylchol ine (1%) were found. Acetylcholine was a very minor choline metabolite in these cells. When placental cells were incubated for 66 h after is olation, they formed syncytiotrophoblasts, which incorporated labeled choline into metabolites in a similar pattern to cytotrophoblasts. The se data indicate that isolated trophoblast cells can metabolize cholin e to form all of its major metabolites and that several metabolites ar e released to the medium in significant amounts. Thus, our data sugges t that the major metabolite supplied to the fetus may be choline, but that betaine and glycerophosphocholine may also be vehicles for transf er of choline equivalents from mother to fetus.