Clues to Why Old Eggs Fail

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Older women are more likely to give birth to children with Down syndrome, a form of mental retardation. The condition is caused by the presence of three copies, rather than the standard two copies, of chromosome 21 in human cells. This problem in chromosome distribution, called meiotic nondisjunction, occurs in the course of the cell division that gives rise to eggs (as well as to sperm). But no one knows how or why meiotic nondisjunction increases as eggs age. The question has been difficult to answer because scientists were unable to develop an animal model in which to study the condition.

Now, Sharon Bickel, Ph.D., a molecular biologist at Dartmouth College in Hanover, New Hampshire, has developed a method that uses fruit flies to gain insight into this puzzle of human biology. Fruit flies continuously produce eggs, but Bickel manipulated the diet of the flies in a way that suspended the maturation of their eggs, allowing them to "age." This mimicked the aging of human eggs.

Studying the "aged" fruit fly eggs, Bickel found that the incidence of meiotic nondisjunction jumped just as it does in older women. Her work also indicated that a back-up genetic system that normally helps to ensure proper chromosome separation and distribution deteriorates as fruit fly eggs age. No one yet knows if the same back-up system exists in humans, or if identical mistakes account for the increased risk of Down syndrome in the children of older mothers. But the fruit fly model system will allow Bickel and others to investigate these important questions.