A model relating the incidence of meiotic trisomy to maternal age

A model is developed to explain the well-documented increase in the incidence of meiotic trisomies with increasing maternal age. This theoretical framework applies to all chromosomes, of which trisomy 21 (responsible for Down's syndrome in humans) is considered as a special case; the model can also be readily extended to trisomies of other mammals. The basic mechanism proposed links the hormonal environment of the oocyte to the durations of certain stages of meiosis. Changes in the hormonal environment, especially through aging, can slow the overall rate of meiosis, lengthening the interval from the resumption of meiosis in dictyotene until anaphase I. This extends the period in which homologous chromosomes are vulnerable to premature separation, increasing the probability of an unequal distribution of chromosomes in the first meiotic division. Testable predictions of the model are presented and discussed.