Could Mothers’ Low Cholesterol Affect Pregnancy?

A study appearing in Human Molecular Genetics is one of the first to suggest that low maternal cholesterol could have an impact on pregnancy, possibly reducing the size of the placenta.

“Recently, there has been considerable interest in understanding contributions of the maternal environment and genotype to fetal development, birth weight, pregnancy outcomes and risks for later disease in the offspring,” said Gail Herman, MD , PhD, director of the Center for Molecular and Human Genetics at The Research Institute and the study’s lead author. “Research has shown that mothers’ high cholesterol during pregnancy is a predictor of heart disease in offspring; however, little is known about the effects of a mother’s low cholesterol on the fetus.”

In this study, pregnant mice with a mutation in a gene called Nsdhl that is needed to make cholesterol were compared with normal pregnant mice. Prior to pregnancy, all of the mice had similar cholesterol levels when fed the same standard, cholesterol-free diet. In both groups of animals, there was a significant drop in cholesterol levels midway through pregnancy. However, the female mice carrying the mutation were slower to regain pre-pregnancy cholesterol levels during the latter part of their pregnancies. When the embryonic placentas were compared in litters of mice carrying the mutations with those from normal mothers, they were found to be significantly smaller. The size of the placenta depended on the status of mother’s Nsdhl gene as well as expression of this gene in the fetal membranes of the yolk sac and placenta. The results suggest that the growing placenta couldn’t access enough cholesterol during this important period, in part, because the mother was unable to produce an adequate amount.

Although there are some important differences between mouse and human gestation, Dr. Herman says this study could have implications for human pregnancy and the function of the human placenta. “Rare, inherited human disorders of cholesterol biosynthesis, such as Smith-Lemli- Opitz syndrome, clearly show that maternal cholesterol is transported to the fetus during human pregnancy, although the extent and duration are not known. These disorders also demonstrate that cholesterol deficiency can have severe adverse effects on normal development,” she said. Dr. Herman says risks of low maternal cholesterol in pregnancy need to be studied further so that they can be better defined.

Cunningham D, Talabere T, Bir N, Kennedy M, McBride KL, Herman GE. Significant Contributions of the Extraembryonic Membranes and Maternal Genotype to the Placental Pathology in Heterozygous Nsdhl Deficient Female Embryos. Hum Mol Genet. 2009 Oct 30. [Epub ahead of print]