CREM, short for cAMP-responsive element modulator, is a transcription factor involved in the cAMP-dependent transcriptional regulation pathway. It plays a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. CREM gene expression gives rise to different isoforms, either activators or repressors of gene expression, which are crucial for regulating gene expression in various biological processes [1].

CREM-mutant mice generated by homologous recombination have revealed significant insights. Spermatogenesis in these mice stops at the first step of spermiogenesis, with late spermatids absent and a ten-fold increase in apoptotic germ cells. Mutant male mice lack spermatozoa, mimicking human infertility cases. This indicates that CREM is vital for normal spermatogenesis, specifically in the differentiation of germ cells into spermatozoa and in maintaining the balance between differentiation and apoptosis in male germ cells [2,3,4].

In conclusion, CREM is a master-switch in regulating male germ cell differentiation and apoptosis, especially in spermatogenesis. The study of CREM-KO mouse models has been instrumental in understanding its role in male infertility, highlighting its significance in this disease area.

References:

1. Lamas, M, Monaco, L, Zazopoulos, E, Foulkes, N S, Sassone-Corsi, P. . CREM: a master-switch in the transcriptional response to cAMP. In Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 351, 561-7. doi:. https://pubmed.ncbi.nlm.nih.gov/8735279/

2. Sassone-Corsi, P. . CREM: a master-switch regulating the balance between differentiation and apoptosis in male germ cells. In Molecular reproduction and development, 56, 228-9. doi:. https://pubmed.ncbi.nlm.nih.gov/10824972/

3. De Cesare, D, Fimia, G M, Sassone-Corsi, P. . CREM, a master-switch of the transcriptional cascade in male germ cells. In Journal of endocrinological investigation, 23, 592-6. doi:. https://pubmed.ncbi.nlm.nih.gov/11079454/

4. Sassone-Corsi, P. . CREM: a master-switch governing male germ cells differentiation and apoptosis. In Seminars in cell & developmental biology, 9, 475-82. doi:. https://pubmed.ncbi.nlm.nih.gov/9813195/