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

Semin Cell Dev Biol. 1998 Aug;9(4):475-82. doi: 10.1006/scdb.1998.0200.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Cell Differentiation / drug effects
  • Cyclic AMP Response Element Modulator
  • DNA-Binding Proteins / physiology*
  • Humans
  • Male
  • Mice
  • Repressor Proteins / physiology
  • Spermatogenesis / drug effects
  • Spermatogenesis / genetics*
  • Spermatogenesis / physiology*


  • DNA-Binding Proteins
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator