Molecular Human Reproduction, Vol. 10, No. 2, pp. 129-135, 2004
© European Society of Human Reproduction and Embryology 2004
Expression of activator of CREM in the testis (ACT) during normal and impaired spermatogenesis: correlation with CREM expression
1Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, 2Institute of Anatomy, Developmental Biology, University of Essen and 3Institute of Reproductive Medicine, University of Muenster and 4Covance Laboratories GmbH, Muenster, Germany
5 To whom correspondence should be addressed at: Institute of Veterinary Anatomy, Histology and Embryology, Frankfurter Strasse 98, 35392 Giessen, Germany. e-mail: Klaus.Steger{at}vetmed.uni-giessen.de
The cAMP-responsive element modulator (CREM) is involved in regulating gene expression in haploid spermatids. Transcriptional activity of the CREM protein is thought to be regulated by activator of CREM in the testis (ACT). Applying RT–PCR and in situ hybridization, cell-specific gene expression of ACT was demonstrated in man, cynomolgus monkey and mouse. During normal spermatogenesis, RT–PCR revealed a strong signal in all three species. We sequenced monkey ACT cDNA and demonstrated that the putative amino acid sequence is highly conserved between these species. In situ hybridization demonstrated ACT mRNA in mid and late pachytene spermatocytes and in round spermatids. Among four infertile men with round spermatid maturation arrest (RSMA), only one patient revealed a strong signal for ACT, while three patients displayed a weak signal for both RT–PCR and in situ hybridization, although germ cells normally expressing ACT were present in these patients. In addition, CREM knockout mice known to be infertile due to RSMA also exhibited only a weak amplification product for ACT cDNA. ACT mRNA was barely detectable in some round spermatids, but was completely absent in pachytene spermatocytes. Database search revealed two and one CRE within the putative human and mouse ACT promoters respectively. Our findings indicate a conserved function of ACT during the evolution of mammalian spermatogenesis and suggest a role for CREM in ACT transcriptional regulation.
Key words: Key words: ACT/human/monkey/mouse/spermatogenesis
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