Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos

Publisher Website
Google Scholar
Abstract
Background Choline is an essential nutrient in methylation, acetylcholine and phospholipid biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a pregnant woman and, subsequently, the developing conceptus at risk for choline deficiency. Methods To determine whether a disruption in choline uptake and metabolism results in developmental abnormalities, early somite staged mouse embryos were exposed in vitro to either an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology. Results Embryos exposed to 250–750 μM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125–275 μM ET-18-OCH3 exhibited similar defects or expansion of the brain vesicles. ET-18-OCH3-affected embryos also had a distended neural tube at the posterior neuropore. Embryonic growth was reduced in embryos treated with either DMAE (375, 500, and 750 μM) or ET-18-OCH3 (200 and 275 μM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 μM ET-18-OCH3 for 6 hr, but there was no evidence of cell death in DMAE-exposed embryos. Conclusions Inhibition of choline uptake and metabolism during neurulation results in growth retardation and developmental defects that affect the neural tube and face. Teratology 64:114–122, 2001.