Colchicine effects on meiosis in the male mouse. II. Inhibition of synapsis and induction of nondisjunction.

This report follows from our earlier study using synaptonemal complex (SC) analysis in which colchicine administered to mouse spermatocytes specifically at leptotene/zygotene blocks synapsis, resulting in univalents at early pachytene. Despite loss of severely damaged cells from the prophase population, substantial numbers of cells with lesser damage progress to late pachytene on schedule. The present study tests whether the surviving cells would continue through meiotic divisions and if so, whether the univalents at MI result in hyperploidy at MII. At 7 days after treatment (late pachytene) 5.9% of the surviving population contains at most four autosomal axial univalents. In whole chromosome preparations 10 days post-colchicine the highest frequency of MIs with univalents is 5.2%. The maximum number of autosomal "chromosomal" univalents per cell is four. The percentage of cells with autosomal univalents at late pachytene, is not significantly different from the percentage of cells with chromosomal univalents at MI. We infer from these observations that the two kinds of univalents are equivalent. At days 11-12 post-colchicine, hyper (and hypo) ploidy at AI-MII is observed. We conclude that univalents produced by colchicine-induced asynapsis at leptotene/zygotene persist and lead to nondisjunction at division I and hyperploidy at division II. If the hyperploid spermatids mature, they would give rise to aneuploid sperm, thus constituting a mechanism for inducing aneuploid (e.g., trisomic) zygotes after fertilization. It is also observed that chiasma frequency (number of chiasmata per bivalent, univalents excluded) is reduced by about 15% of the control. Nondisjunction is known to be the endpoint of colchicine action when administered at prometaphase-MI, interfering with the segregation of homologues through effects on the MI-AI spindle. We show that nondisjunction is also the endpoint of colchicine's effect at early pachytene, in this case causing synaptic inhibition that creates univalents which are then distributed randomly at first division. These conclusions draw special attention to predivision meiotic events, particularly those affecting synapsis, and their sensitivity to induced and/or inherent effects that may have consequences later at meiotic divisions, creating risk to the chromosomal constitution of the gametes.