An hypothesis regarding the origin of aneuploidy in man: indirect evidence from an experimental model.

Abstract

Recent studies have clearly demonstrated that aneuploidy may be induced in about 10 to 20% of oocytes and recently ovulated eggs when female mice are given an intragastric injection of a dilute solution of ethanol. Similar rates of aneuploidy have also been observed when recently ovulated eggs are briefly exposed in vitro to a dilute solution of ethanol in tissue culture medium. These findings are briefly reviewed, and observations made on the possible underlying mechanism of induction of chromosome malsegregation in the ethanol exposed groups. Attention is drawn to evidence from a wide range of studies on the effect of ethanol, acetaldehyde (its primary metabolite), and anaesthetics on cell division and chromosome segregation in an attempt to substantiate an hypothesis regarding the mode of action of these agents. In the light of this information, it is hypothesised that exposure to ethanol probably interferes with the normal functioning of the cytoskeletal elements of the spindle apparatus, or its precursor elements, during the first or second meiotic divisions. An attempt is also made to account for the very high incidence of aneuploid conceptuses in man, a high proportion of which are spontaneously aborted. It is hypothesised that exposure to ethanol and other spindle active agents during appropriate stages of oogenesis (in particular during the first meiotic division), and possibly also during spermatogenesis, may be important aetiological factors in a proportion of those cases of spontaneous abortion with a numerical chromosome anomaly for which no other obvious cause is recognised. If it is valid to extrapolate from these experimental findings to the clinical situation in man, it is suggested that attention should also be drawn to the potentially greater hazard to the conceptus which could result from maternal alcohol consumption at and shortly before conception.