Congenital Malformations

Most of the genes studied by Nüsslein-Volhard, Wieschaus and Lewis have important functions during the early development of the embryo. They control formation of the body axis which means the polarity of the embryo, the segmentation of the body, e.g. the vertebral column, and the specialization of individual segments into different organs like ribs, pelvis and extremities. It is likely that mutations in such important genes are responsible for some of the early, spontaneous abortions that occur in man, and for some of the about 40 % of the congenital malformations that develop due to unknown reasons. We do not know how frequent spontaneous abortions are, since most of them occur before the woman realizes that she is pregnant. Calculations indicate, however, that only 6 of 20 fertilized eggs result in fully developed children, less than one third of all pregnancies begun.

Environmental factors such as very high doses of vitamin A during early pregnancy are also known to disturb the regulation of HOX genes, thus inducing severe congenital malformations as hydrocephalus, lesions in the vertebral column and heart diseases. Vitamin A given in high doses during pregnancy alters the expression of genes both in mice and men. Experiments with mouse embryos confirm this, as you can see on the poster. The mothers of two of the embryos were given vitamin A (retinoic acid) in high doses for 8 days. The embryo in the middle has lost several vertebrae and the embryo to the right has got no posterior region.

In 1995 a Boston University School of Medicine study of 22 000 mothers stated that overdosage of vitamin A as low as three times the recommended dose during the first trimester of the pregnancy may cause fetal damage. The scientists found, however, that most of the women in the study (98,6 %) had an intake of the vitamin without risk. Since the vitamin A-content of liver is high, pregnant women are recommended not to eat too much of that food. Certain drugs, e.g. for treatment of severe acne, contain vitamin A which calls for caution by fertile women. In Sweden the National Board of Health and Welfare prescribes special routines for such cases, including contraceptive pills.

There are also other substances in our environment, both known and unknown, that disturb embryonic development, and that thus cause spontaneous abortions or congenital malformations.