SPERMIOGENESIS DEFICIENCY AND GERM-CELL APOPTOSIS IN CREM-MUTANT MICE

Spermiogenesis is a complex process by which postmeiotic male germ cel ls differentiate into mature spermatozoa. This process involves remark able structural and biochemical changes including nuclear DNA compacti on and acrosome formation(1,2). Transcriptional activator CREM (cyclic AMP-responsive element modulator) is highly expressed in postmeiotic cells(3-5), and CREM may be responsible for the activation of several haploid germ cell-specific genes involved in the structuring of the sp ermatozoon(5-7). The specific role of CREM in spermiogenesis was addre ssed using CREM-mutant mice generated by homologous recombination. Ana lysis of the seminiferous epithelium in mutant male mice reveals postm eiotic arrest at the first step of spermiogenesis. Late spermatids are completely absent, and there is a significant increase in apoptotic g erm cells. We show that CREM deficiency results in the lack of postmei otic cell-specific gene expression. The complete lack of spermatozoa i n the mutant mice is reminiscent of cases of human infertility.