The CREM system in human spermatogenesis.

Spermatogenesis is a multi-step process, regulated by endocrine, paracrine and autocrine signals, through which immature germ cells differentiate into spermatozoa. The cAMP-dependent transcription factor CREM directs in the testis the expression of genes related to the structuring of mature spermatozoa. CREM gene expression originates different isoforms, which in turn can be divided into activators or repressors of gene expression. Whereas only CREM repressors are expressed in pre-meiotic germ cells in mice, a switch to the expression of the CREM activator tau occurs in post-meiotic germ cells. In addition, mice lacking CREM gene are infertile and present an arrest of germ cell maturation at the stage of round spermatid. We have demonstrated that CREM gene is expressed also in human germ cells and that a switch from the expression of repressors to activators is present in normospermic men. In particular, CREM tau mRNA is located in the cytoplasm of round spermatids. Conversely, in patients showing a testicular pattern of round spermatid maturation arrest only CREM repressors are expressed. Other reports have confirmed our data, supporting the hypothesis that CREM plays a role also in human spermatogenesis and that the absence of "the CREM switch" can be associated to spermatogenic arrest.