CREM: a master–switch governing male germ cells differentiation and apoptosis

Abstract

Several endocrine and neuronal functions are governed by the cAMP–dependent signalling pathway. In eukaryotes, transcriptional regulation upon stimulation of the adenylyl cyclase signalling pathway is mediated by a family of cAMP–responsive nuclear factors. The CREM gene plays a key physiological and developmental role within the hypothalamic–pituitary–gonadal axis. CREM is highly expressed in postmeiotic cells upon a striking developmental switch regulated by the pituitary hormone FSH. CREM–mutant mice generated by homologous recombination reveal that spermatogenesis stops at the first step of spermiogenesis. Late spermatids are completely absent while there is a significant increase in apoptotic germ cells. A series of post–meiotic germ cell–specific genes are not expressed. Mutant male mice completely lack spermatozoa. This phenotype is reminiscent of cases of human infertility.