HSP70-2 IS REQUIRED FOR DESYNAPSIS OF SYNAPTONEMAL COMPLEXES DURING MEIOTIC PROPHASE IN JUVENILE AND ADULT-MOUSE SPERMATOCYTES

Spermatogenic cells synthesize a unique 70-kDa heat shock protein (HSP 70-2) during prophase of meiosis I, and targeted disruption of the Hsp 70-2 gene has shown that this protein is required for spermatogenic c ell differentiation in adult mice, HSP70-2 is associated with synapton emal complexes formed between paired homologous chromosomes during mei otic prephase, The present study focuses on the nearly synchronous fir st wave of spermatogenesis in 12- to 28-day old juvenile mice to deter mine more precisely when HSP70-2 is required and what meiotic processe s are affected by its absence. Spermatogenesis in homozygous mutant mi ce (Hsp70-2(-/-)) proceeded normally until day 15 when increasing numb ers of pachytene spermatocytes became apoptotic and differentiation of cells beyond the pachytene stage began to falter, Synaptonemal comple xes assembled in Hsp 70-2(-/-) mice and spermatocytes developed throug h the final pachytene substage, However, synaptonemal complexes failed to desynapse and normal diplotene spermatocytes were not observed, Me taphase spermatocytes were not seen in tissue sections from testes of Hsp70-2(-/-) mice, and expression of mRNAs and antigens characteristic of late pachytene spermatocytes (e.g., cyclin Al) and development of spermatids did not occur. Thus, HSP70-2 is required for synaptonemal c omplex desynapsis, and its absence severely impairs the transition of spermatogenic cells through the late meiotic stages and results in apo ptosis beginning with the first wave of germ cell development in juven ile mice.