An experimental approach to the analysis of mechanisms of meiotic nondisjunction and anaphase lagging in primary oocytes.

The in vivo genomic mutagenicity of colchicine in Chinese hamster primary oocytes was analyzed at a carefully chosen dose that did not completely arrest the formation of the first meiotic spindle but exhibited a remarkable ability to induce nondisjunction, very possibly as a result of inhibition of tubulin polymerization. A single dose of 3 microgram of colchicine per gram body weight was administered intraperitoneally at the onset of formation of the first meiotic spindle in females with a normal estrous cycle. Morphologically abnormal secondary oocytes with one or two extremely large first polar bodies occurred frequently, namely, in 47 (11.3%) of 416 oocytes. Chromosome analysis of a total of 2,124 secondary oocytes revealed that the overall incidence of aneuploids increased significantly (P less than 0.001) in the experimental group (25.9%, or 99/382) as compared with the control group (2.0%, or 35/1,742). The minimum genomic mutagenicity of colchicine caused non-disjunction in one or two bivalents and eventually induced the formation of aneuploid secondary oocytes with chromosome numbers within the haploid range. The maximum genomic mutagenicity at the selected dose caused the elimination of a large number of chromosomes from the egg body, in association with the formation of a giant polar body or bodies. Three types, each with two subdivisions, of abnormal chromosome segregation between the oocytes and their giant polar body or bodies were studied, revealing part of the process resulting in aneuploid production due to either nondisjunction or anaphase lagging. The fate of the lagging chromosomes was also observed; they were included in neither the oocytes nor the polar body but eventually degenerated within the perivitelline space. The conditions of the spindle in oocytes aged by pre- and postovulatory over-ripeness, both of which have been known to induce meiotic chromosomal nondisjunction, are discussed in relation to tubulin polymerization.