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

Teratology. 2001 Aug;64(2):114-22. doi: 10.1002/tera.1053.


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-OCH(3)). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology.

Results: Embryos exposed to 250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the brain vesicles. ET-18-OCH(3)-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 microM) or ET-18-OCH(3) (200 and 275 microM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Animals
  • Anti-Dyskinesia Agents / toxicity*
  • Choline / antagonists & inhibitors*
  • Choline / metabolism*
  • Deanol / toxicity*
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / pathology
  • Embryonic and Fetal Development / drug effects*
  • Female
  • Male
  • Mice
  • Neural Tube Defects / chemically induced*
  • Neural Tube Defects / embryology
  • Neural Tube Defects / pathology
  • Organ Culture Techniques
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / toxicity
  • Phospholipid Ethers / pharmacology
  • Phospholipid Ethers / toxicity
  • Pregnancy


  • Anti-Dyskinesia Agents
  • Phosphodiesterase Inhibitors
  • Phospholipid Ethers
  • edelfosine
  • Deanol
  • Choline