Non-disjunction in aging female mice

Classical studies have shown that reproductive performance declines with maternal age in humans and other mammals. There is an increase of trisomic offspring with maternal age in humans and an increase of trisomic embryos and fetuses with maternal age in mice. It has been suggested that this increase in non-disjunction is due to the decrease in chiasma frequency arid increase in univalents observed in the oocytes of old mice. This study was undertaken to determine the effects of maternal age on non-disjunction in the oocytes of CBA mice. Oocytes from CBA mice varying in age from two to eleven months were cultured to the metaphase II stage of meiosis and the chromosomes were analysed. The oocytes from three maternal age groups were compared with respect to the mean number of oocytes obtained per mouse, the frequency of maturation to metaphase II, and the frequency of numerical chromosome abnormalities. Both the mean number of oocytes obtained per mouse and the frequency of maturation decreased markedly with maternal age. The frequency of chromosome abnormalities in the oocytes increased with maternal age from the young to the middle aged mice but dropped off in the oldest maternal age group. No hyper-ploid (n+1) oocytes were observed in the young or old group of mice but 4.9% hyperploidy occurred in the middle age group. It is suggested that the lack of hyperploid oocytes in the old CBA females might be due to a threshold effect in which oocytes which are damaged by the number or type of univalents become atretic and do not progress to metaphase II. The frequency of diploid (2n) oocytes was 1.7% and was not maternal age dependent. An overall theory of maternal age related nondisjunction is proposed in which the various environmental and genetic factors known to affect non-disjunction are linked to an underlying mechanism of univalent production in oocytes.Medicine, Faculty ofMedical Genetics, Department ofGraduat