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Choline Deficiency May Hinder Fetal Brain Development

Choline deficiency alters the proliferation of endothelial cells (arrow) in the developing hippocampus of a mouse.Mehedint et al. PNAS.

Lack of choline during pregnancy may lead to reduced blood vessel growth in the brain of the developing fetus, a new study in mice suggests. The finding adds new information about the importance of choline for prenatal brain development.

Choline is an essential nutrient that's needed to make cell membranes and the nerve cell messenger acetylcholine. Foods that are rich in choline include milk, eggs, liver and peanuts. For more than a decade, choline has been recognized as a key nutrient for fetal development during pregnancy. However, it’s estimated that less than 15% of pregnant women in the United States get enough choline in their diets.

In earlier research, Dr. Steven H. Zeisel of the University of North Carolina at Chapel Hill found that maternal choline deficiency alters the growth of new nerve cells in the hippocampus of fetal mice. Because the developing brain also depends on an adequate blood supply, Zeisel and his colleagues decided to take a closer look at choline’s effect on the growth of new blood vessels, or angiogenesis, in the fetal hippocampus. Their research was supported by NIH’s National Institute on Aging (NIA), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Environmental Health Sciences (NIEHS).

The researchers fed pregnant mice either a choline-deficient diet, a standard amount of choline or a choline-enriched diet. The results appeared in the July 20, 2010, edition of the Proceedings of the National Academy of Sciences. By the 17th day of development, the choline-deficient fetal mice had significantly fewer blood vessels in the hippocampus compared to the mice whose mothers received a standard or choline-enriched diet. The fetal hippocampus in choline-deficient mice also had less proliferation of endothelial cells, the cells that line the inner walls of blood vessels.

Further experiments linked choline deficiency to an overexpression of 2 growth factors—called Vegfc and Angpt2—in the fetal hippocampus. These growth factors regulate angiogenesis and the maturation of endothelial cells. The researchers propose that the abundance of the growth factors in the hippocampus during choline deficiency leads to the rapid differentiation and maturity of endothelial cells. Because differentiated cells divide less frequently, or not at all, the changes may prematurely dampen the growth of new blood vessels.

The findings add to our understanding of choline’s effects on the developing brain. “The study could impact prenatal care in humans, as many pregnant women in the United States eat diets that contain less choline than recommended by authorities,” says the paper’s lead author, Dr. Mihai G. Mehedint.

The researchers are now conducting clinical trials to learn more about how much choline people need and how requirements may vary from person to person. Their studies of choline intake during and after pregnancy have found that the mother’s genetic makeup can affect choline levels in blood and breast milk.

—by Vicki Contie