CREM: a transcriptional master switch during the spermatogenesis differentiation program.

Spermatogenesis is a complex differentiation process under the hormonal control of the hypothalamic-pituitary axis. The CREM gene encodes activators and repressors of cAMP-mediated gene transcription. The transcript corresponding to the activator isoform CREMtau is found at high levels in pachytene spermatocytes onwards. The CREMtau protein, however, is present only in post-meiotic spermatids where it activates the transcription of testis-specific genes, such as the protamines and transition proteins. Mice in which the CREM gene has been inactivated by homologous recombination have been generated. Homozygous male mutant mice are sterile and produce no spermatozoa. Histological analysis of the seminiferous tubules reveal a complete arrest of spermatogenesis at the first step of spermiogenesis. CREM deficiency results in the lack of post-meiotic gene expression and a ten-fold increase in apoptotic germ cells. These results demonstrate the essential role of CREM in spermatogenesis and are reminiscent of some cases of male infertility.