What are the spermatocyte's requirements for successful meiotic division?

The consequences of error during meiotic division in spermatogenesis can be serious: aneuploid spermatozoa, embryonic lethality, and developmental abn ormalities. Recombination between homologs is essential to ensure normal se gregation; thus the spermatocyte must time division precisely so that it oc curs after recombination between chromosomes and accumulation of the cell-c ycle machinery necessary to ensure an accurate segregation of chromosomes. We use two systems to investigate meiotic division during spermatogenesis i n the mouse: pharmacological induction of meiotic metaphase in cultured spe rmatocytes and transillumination-mediated dissection of stage XII seminifer ous tubule segments to monitor progress through the division phase. By thes e approaches we can assess timing of acquisition of competence for the meio tic division phase and the temporal order of events as division proceeds. C ompetence for the meiotic division arises in the mid-pachytene stage of mei otic prophase, after chromosomes have synapsed and coincident with the accu mulation of the cell-cycle regulatory protein CDC25C. The activity of both MPF and topoisomerase II are required. The earliest hallmarks of the divisi on phase are nuclear envelope breakdown, followed by phosphorylation of his tone H3 and chromosome condensation. These events are likely to be monitore d by checkpoint mechanisms since checkpoint proteins can be localized in nu clei and DNA-damaging agents delay entry into the meiotic division phase. U nderstanding how the spermatocyte regulates its entry into the meiotic divi sion phase can help clarify the natural mechanisms ensuring accurate chromo some segregation and preventing aneuploidy. (C) 1999 Wiley-Liss, Inc.