The teratogenic effects of alcohol following exposure during pregnancy, and its influence on the chromosome constitution of the pre-ovulatory egg.

Much information has emerged over the years concerning the teratogenicity of acute and chronic alcohol exposure during pregnancy. Both alcohol and its primary metabolite, acetaldehyde, are teratogenic. Exposure during pregnancy may lead to fetal alcohol syndrome (FAS), and this is said to occur in a substantial proportion of infants born to mothers who are chronic, heavy daily drinkers. Such infants usually survive to birth but are mentally retarded, often display growth retardation and additionally display a characteristic range of clinical features, principally craniofacial abnormalities and neurological damage. We have recently been interested in the effect of exposure of pregnant female mice to a single high level of alcohol during pregnancy, equivalent to an episode of 'binge' drinking, on the optic nerve, and believe that our findings, which are outlined in the first part of this review, may shed important light on the pathogenesis of some of the ocular features characteristically seen in infants with this syndrome. What is not generally appreciated, is that exposure to alcohol and other 'spindle-active' substances that have a similar action on the meiotic spindle apparatus during the menstrual cycle before conception can induce chromosome segregation errors in the ovulated oocyte. The successful fertilization of such eggs consequently results in the production of aneuploid embryos, which have a very high chance of being spontaneously aborted during the first trimester of pregnancy. Those relatively few aneuploid conceptuses that survive to term invariably show moderate to severe degrees of mental retardation, craniofacial and other abnormalities, as well as having a significantly reduced life expectancy. The findings from our experimental studies that have been carried out in mice draw attention to important principles which are of general applicability to the situation in the human. These findings, and our conclusions drawn from them, are discussed in detail in the second part of this review.