COLCHICINE EFFECTS ON MEIOSIS IN THE MALE-MOUSE .1. MEIOTIC PROPHASE - SYNAPTIC ARREST, UNIVALENTS, LOSS OF DAMAGED SPERMATOCYTES AND A POSSIBLE CHECKPOINT AT PACHYTENE

Antimitotic agents administered at the time of synapsis (leptotene/zyg otene) have been shown to induce synaptic abnormalities visible during pachytene in the male mouse. The object of this study was to test the hypothesis that cells with relatively large amounts of colchicine-ind uced damage to the synaptonemal complex (SC) are eliminated from proph ase whereas cells with relatively small amounts of SC damage proceed t hrough to the end of prophase. Male mice were injected with tritiated thymidine to mark a cohort of spermatocytes at premeiotic S-phase for tracking through pachytene. Forty-eight hours later, when those cells were at leptotene/zygotene, colchicine was administered intratesticula rly. Whole-mount SC spreads were made from animals sacrificed at vario us times following colchicine administration, and prepared for autorad iography. The marked cells were examined by light and electron microsc opy and the kind and number of synaptic abnormalities were scored thro ughout pachytene. Colchicine-induced SC damage included single axial e lements (univalents), together with partially synapsed and nonhomologo usly synapsed SCs. The amount of SC damage (amount and type per cell a nd frequency of cells with damage) scored at early pachytene exceeded by three-to fivefold the amount at late pachytene. This is consistent with spermatogenic cell loss from the seminiferous tubule via colchici ne-induced destruction of Sertoli cell microtubules. The presence of s permatocytes with no more than four autosomal univalents at late pachy tene indicates that some cells with low amounts of synaptic damage pro gress to the end of pachytene. The loss of the most severely damaged c ells may represent a meiotic checkpoint at early pachytene in the male mouse.